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 Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System (NCT03643562), a na phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03643562 |
| Phase | Phase 3 |
| Condition | Niemann-Pick Type C Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 27 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mandos LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with Niemann-Pick Type C disease and neurologic manifestations were enrolled. The primary outcome population is described as all enrolled participants. The registry distinguishes participants who had not previously taken adrabetadex from those who had already received it.
Intervention
The intervention was adrabetadex administered by intrathecal injection every 2 weeks. Participants already taking the drug continued at a stable dose; participants who had never taken it were to start at 400 mg, according to the study description.
Comparator
There was no randomized control group. Treatment-naive and previously treated participants are described separately, but the registry cautions that these are not like-for-like control groups. Their event counts therefore do not establish a treatment contrast.
Primary question
The primary outcome counts participants with treatment-emergent adverse events and serious adverse events from baseline up to Week 134. It describes how many participants experienced these events during the stated observation period, rather than measuring a comparative treatment effect.
3. Trial Design
This was a Phase 3, open-label, single-group study of adrabetadex for participants with neurologic manifestations of Niemann-Pick Type C disease. The registry lists enrollment of 27 and identifies Mandos LLC as the sponsor. Allocation is listed as not applicable, and masking is listed as none. These design features mean that the study record does not describe random assignment or blinded treatment.
The study description says it was amended from expanded access to a clinical trial. Participants received prescribed adrabetadex by intrathecal injection every 2 weeks. Those already taking the drug were to receive their stable dose, while those who had never taken it were to start at 400 mg. Treatment was described as continuing until the participant’s doctor found that it no longer helped, the participant withdrew, or the study stopped for any reason. Participants were not to receive additional study treatment after participation in the protocol.
The registry lists the study as terminated. The study start is recorded as 2018-06-18, and primary completion as 2021-11-02. The reason for termination is not reported in the registry record. The primary outcome is a safety count, not a randomized comparison of treatment with a control. The two reported participant categories—treatment naive and previously treated—are not equivalent to randomized arms, and differences between their counts should not be interpreted as causal effects.
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 | Treatment Naive | Previously Treated |
|---|---|---|
| STARTED | 9 | 18 |
| Received at Least 1 Dose of Study Drug | 9 | 18 |
| COMPLETED | 1 | 2 |
| NOT COMPLETED | 8 | 16 |
Reasons for not completing this period:
| Reason | Treatment Naive | Previously Treated |
|---|---|---|
| Adverse Event | 1 | 0 |
| Lack of Efficacy | 0 | 1 |
| Physician Decision | 0 | 1 |
| Study Terminated by Sponsor | 2 | 10 |
| Withdrawal by Subject | 2 | 2 |
| Other than specified | 3 | 2 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants
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 enrolled participants
| Characteristic | Unit | Treatment Naive | Previously Treated | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 18 | 27 | |
| Age, Continuous | years | 12.33 (SD 8.718) | 17.94 (SD 13.705) | 16.07 (SD 12.388) |
| Sex: Female, Male: Female | Participants | 4 | 7 | 11 |
| Sex: Female, Male: Male | Participants | 5 | 11 | 16 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 | 18 | 26 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 7 | 17 | 24 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over Baseline up to Week 134.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), with the timeframe given as baseline up to Week 134. A TEAE is defined in the registry as an adverse event with onset on or after adrabetadex treatment began. An adverse event is any untoward medical occurrence in a participant who received study drug, regardless of whether a causal relationship to the drug is considered possible.
The registry defines an SAE by specified serious outcomes, including death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or another important medical event that jeopardized the participant and required medical intervention to prevent one of those outcomes. The endpoint is used to describe safety experiences during treatment; it does not, by itself, establish that treatment caused an event.
Counting affected participants gives a direct description of how many people in the stated population experienced events. It does not report event timing, duration, recurrence, severity beyond the serious-event classification, or a comparative risk estimate. The record also refers readers to its reported adverse-event information for other non-serious events and all serious events, regardless of causality.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted results describe adverse events among participants treated in an open-label, single-group study. In the treatment-naive category, 5 of 9 participants at risk had a serious adverse event, and 9 of 9 had another adverse event. In the previously treated category, 9 of 18 participants at risk had a serious adverse event, and 17 of 18 had another adverse event. The record lists 0 deaths in each category. These are descriptive counts, not estimates from a randomized comparison.
The distinction between serious and other adverse events matters. Seriousness is defined by the registry using outcomes such as life-threatening events and hospitalization; it is not a judgment that the study drug caused an event. The broader adverse-event definition also does not require a causal link. Thus, the counts indicate events reported in participants who received study drug, but they do not distinguish events attributable to treatment from events arising for other reasons.
The registry lists acute respiratory failure at 22.2%, seizure at 16.7%, and deafness, vomiting, meningitis, and pneumonia at 11.1% each among the top serious-event terms. Those percentages are registry-reported values; the record excerpt does not give event counts for each term. It would be inappropriate to infer those counts or to treat the percentages as comparative estimates.
The separately reported treatment-naive and previously treated categories should not be read as intervention and control groups. Their prior treatment histories differ, and the record explicitly notes that the groups are not a like-for-like control comparison. The counts alone cannot show whether event patterns differ because of adrabetadex, underlying disease, prior treatment, observation, or other factors.
No inferential analysis is listed in the record. It does not report confidence intervals, p-values, adjusted estimates, or a treatment-effect estimate for this endpoint. A confidence interval, as a general statistical concept, expresses the uncertainty around an estimated quantity; without a reported estimate and interval, the precision of a comparative effect cannot be assessed. The event counts are therefore most useful as a description of the recorded safety experience in this study, not as proof of benefit, harm, or causation.
9. Statistical Methods Explained
What kind of outcome is this? The primary outcome is a participant count for a binary event status: whether a participant experienced a qualifying adverse event during the stated timeframe. This is different from counting every event episode. A participant with repeated events may still contribute as a participant with an event, while the record’s primary outcome description does not provide episode-level frequency.
General statistical explanation: for a binary outcome, a study can report the number of participants who experienced the event and the number considered at risk or observed. Such counts are descriptive. A comparison between groups requires an appropriate design and analysis, and it is particularly difficult to interpret causally when group membership reflects prior treatment rather than random assignment. In this record, the registry warns that the treatment-naive and previously treated categories are not like-for-like controls.
What does the single-group design imply? The study is listed as single-group, with allocation not applicable and no masking. The two displayed participant categories do not change that design description. Because the record does not describe random assignment to adrabetadex or a control treatment, observed event counts cannot isolate the effect of treatment from other explanations. Open-label treatment also means the study was not masked, as recorded; the registry record does not describe blinded assessment.
General statistical explanation: randomization can help balance measured and unmeasured factors between comparison groups, while masking can reduce some differences in expectations and assessment. These design features do not guarantee that results are unbiased, but their absence limits the strength of causal interpretation. This is a limitation on what can be concluded from the design, not a claim about any particular event’s cause.
How should event counts be read? The primary endpoint counts participants with TEAEs and SAEs, and the registry separately reports participants at risk and participants affected in the treatment-naive and previously treated categories. The count of affected participants describes occurrence in those recorded categories. The record does not provide a time-to-event analysis, person-time, event duration, or a model accounting for differences in exposure duration. Treatment was described as continuing under specified stopping conditions, so the available record does not establish that each participant had the same treatment exposure or observation time.
General statistical explanation: when observation time differs, a simple count may not capture the rate at which events occur over time. Analyses using time or exposure information can address different questions, but the record does not report such an analysis for this endpoint. Nor does it report adjusted comparisons or uncertainty intervals. Therefore, neither a rate comparison nor an adjusted treatment effect should be inferred from the counts.
What is absent from the analysis record? The registry lists 1 outcome measure and 0 analyses. It does not report inferential methods for the primary endpoint, an analysis population beyond the endpoint’s description as all enrolled participants, or a method for handling repeated events. It also does not report confidence intervals, p-values, covariate adjustment, or sensitivity analyses for this outcome. Statistical significance and precision cannot be assessed from the posted counts alone.
General statistical explanation: a confidence interval communicates the uncertainty associated with an estimate, while a p-value evaluates compatibility with a specified null hypothesis under an analysis model. Neither replaces consideration of study design, outcome definitions, or bias. Since neither is reported for the primary outcome, readers should not infer that a difference is statistically significant or precise.
How should planning illustrations be understood? Any sample-size illustrations associated with the posted results are planning exercises, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the planning effect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for 80% or 90% power, where those planning levels are shown. They are not the study’s own design justification, and the registry record does not report that those assumptions were used to plan this study.
Because the study is not a randomized comparison and its participant categories are not like-for-like controls, a planning illustration based on an observed contrast should not be mistaken for evidence that the contrast is causal. General statistical explanation: power is a design quantity tied to an assumed effect and analysis; it is not a measure of how likely a result already observed is to be true. The registry record does not report a sample-size justification, an interim-analysis plan, or a statistical analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 1 outcome measure and 0 analyses. The primary measure combines the count of participants with TEAEs and SAEs in its title, but the record excerpt does not describe a multiplicity procedure or a hierarchy for testing outcomes. No multiplicity adjustment is reported in the registry record. Since no inferential analyses are listed, the record does not provide a set of hypothesis tests from which to assess how multiplicity was handled.
Missing-data methods are not reported in the registry record. The available description does not state how missing safety observations, incomplete follow-up, or participants who stopped treatment were handled in the endpoint analysis. The study description permits treatment to stop under specified circumstances, but it does not provide participant-level follow-up or outcome-completion information. No imputation method or sensitivity analysis is reported.
The primary endpoint identifies all enrolled participants as its population. The adverse-event summaries separately identify treatment-naive and previously treated categories and report participants at risk and affected. The record does not give additional details about analysis-set definitions, exclusions, or how participants with incomplete information were classified. These omissions limit assessment of whether the reported counts represent complete observation over the stated timeframe.
General statistical explanation: multiplicity matters when many outcomes or tests are examined because repeated testing can increase the chance of an apparently notable result. Missing-data handling matters because the observed participants may not fully represent those with incomplete follow-up. Neither issue can be resolved from the posted counts alone. The registry record does not report a statistical plan addressing these questions.
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 |
|---|---|---|---|
| Treatment Naive | 5 | 9 | 55.6% |
| Previously Treated | 9 | 18 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Naive | 0 of 9 |
| Previously Treated | 0 of 18 |
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 |
|---|---|
| Treatment Naive | 9 of 9 |
| Previously Treated | 17 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Naive | Previously Treated |
|---|---|---|---|
| Seizure | Nervous system disorders | 1 of 9 | 3 of 18 |
| Pneumonia | Infections and infestations | 1 of 9 | 2 of 18 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 9 | 0 of 18 |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 2 of 18 |
| Ventricular extrasystoles | Cardiac disorders | 0 of 9 | 1 of 18 |
| Deafness | Ear and labyrinth disorders | 1 of 9 | 0 of 18 |
| Constipation | Gastrointestinal disorders | 0 of 9 | 1 of 18 |
| Crohn's disease | Gastrointestinal disorders | 0 of 9 | 1 of 18 |
| Vomiting | Gastrointestinal disorders | 1 of 9 | 0 of 18 |
| Cholangitis | Hepatobiliary disorders | 0 of 9 | 1 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Naive | Previously Treated |
|---|---|---|---|
| Fatigue | General disorders | 6 of 9 | 7 of 18 |
| Upper respiratory tract infection | Infections and infestations | 3 of 9 | 8 of 18 |
| Ataxia | Nervous system disorders | 5 of 9 | 6 of 18 |
| Vomiting | Gastrointestinal disorders | 4 of 9 | 4 of 18 |
| Hypoacusis | Ear and labyrinth disorders | 2 of 9 | 4 of 18 |
| Pyrexia | General disorders | 3 of 9 | 3 of 18 |
| Headache | Nervous system disorders | 3 of 9 | 2 of 18 |
| Somnolence | Nervous system disorders | 0 of 9 | 4 of 18 |
| Constipation | Gastrointestinal disorders | 2 of 9 | 1 of 18 |
| Diarrhoea | Gastrointestinal disorders | 0 of 9 | 3 of 18 |
Serious events with the highest arm-level rate: acute respiratory failure (22.2%), seizure (16.7%), deafness (11.1%), vomiting (11.1%), meningitis (11.1%).
The registry reports serious adverse events for 5 of 9 participants at risk in the treatment-naive category and 9 of 18 in the previously treated category. It reports other adverse events for 9 of 9 and 17 of 18, respectively. The death count is 0 in both categories. These figures describe participants in the registry’s stated categories; they are not evidence of a causal treatment effect.
The serious-event terms listed include acute respiratory failure at 22.2%, seizure at 16.7%, and deafness, vomiting, meningitis, and pneumonia at 11.1% each. These are the percentages reported by the registry. The accompanying record does not provide term-specific counts in this summary, and the listed percentages should not be converted into counts or interpreted as comparisons between groups.
The registry’s adverse-event definition does not require a suspected relationship to adrabetadex. A serious event is classified by its nature or consequences, not by whether the drug caused it. The figures therefore summarize reported safety events during the study; they do not establish causality. The record’s stated timeframe for the primary outcome is baseline up to Week 134, but it does not report participant-specific exposure or follow-up durations.
12. What the Result Does, and Does Not, Mean
The results describe safety events recorded in an open-label study of adrabetadex among participants with Niemann-Pick Type C disease and neurologic manifestations. The primary endpoint counts participants with treatment-emergent adverse events and serious adverse events from baseline up to Week 134. The event summaries give counts for treatment-naive and previously treated participants and report no deaths in either category.
These results do not establish that adrabetadex caused the events. The registry defines adverse events without regard to causal relationship, and it describes serious events by their seriousness criteria. The results also do not establish that treatment prevented or reduced events. There is no randomized control group against which to compare the observed counts, and the registry cautions that the treatment-naive and previously treated categories are not like-for-like controls.
The record does not report an inferential analysis, a confidence interval, or a p-value for the primary outcome. As a result, the precision of any comparative effect cannot be evaluated from the registry information. The counts should be understood as descriptive observations in the study, not as a definitive estimate of treatment risk relative to another treatment or no treatment.
The study description says information would be collected about long-term safety and effectiveness, but the listed primary outcome is safety-focused. The registry does not report a primary efficacy result in the registry record recorded for this study. Nor does it report the reason for termination, missing-data methods, or a statistical analysis plan. Those limits make it important to distinguish the study’s stated objective and observed safety summaries from conclusions that would require additional analyses or a suitable comparison group.
General statistical explanation: a descriptive count can be informative about the types of events observed, but causal interpretation depends on design, measurement, follow-up, and analysis. The available registry record supports reading these figures as reported events in study participants, with substantial limits on comparative and causal conclusions.
13. Why This Trial Matters Statistically
This study is statistically important because it illustrates how safety information can be presented when there is no randomized control group. The record distinguishes treatment-naive participants from participants who had previously taken adrabetadex, but explicitly warns that these categories are not like-for-like controls. Keeping that distinction visible helps prevent descriptive subgroup counts from being mistaken for a treatment comparison.
The endpoint also shows why outcome definitions matter. A TEAE is defined by onset on or after treatment starts, while an SAE is defined by seriousness criteria. The registry’s general adverse-event definition does not require a suspected causal relationship. Readers therefore need to separate whether an event occurred, whether it met the serious-event definition, and whether there is evidence that treatment caused it. The posted counts address the first two questions, not the third.
The registry lists 1 outcome measure and 0 analyses. That makes transparency about what is and is not estimated especially important. Counts provide a direct description, but without reported inferential methods or uncertainty intervals, they do not quantify the precision of a comparative effect. The record also does not report multiplicity procedures, missing-data methods, or a statistical analysis plan.
General statistical explanation: clinical evidence is shaped by both the design and the analysis. A careful interpretation does not demand more from descriptive safety data than they can support. In this case, the registry can inform readers about the safety outcomes recorded during the study, while the single-group design and absent inferential analyses limit conclusions about relative safety and causation.
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 study is open-label and single-group, with allocation listed as not applicable and masking listed as none. There is no randomized control group. Although the registry presents treatment-naive and previously treated categories separately, it explicitly says those categories are not a like-for-like control comparison. Differences in their event counts cannot be attributed to treatment history or treatment effect from these data alone.
The study description allows treatment to end if the doctor finds it no longer helps, if a participant withdraws, or if the study stops. The record does not report participant-level exposure duration, follow-up completeness, or how early stopping affected safety observation. The reason for the study’s terminated status is not reported in the registry record.
The primary endpoint is a count of participants with TEAEs and SAEs. The record does not report event timing, duration, recurrence, exposure-adjusted rates, confidence intervals, p-values, adjusted estimates, or inferential analyses. It does not report methods for missing safety data, an analysis-set definition beyond all enrolled participants, or sensitivity analyses. The registry also does not report a statistical analysis plan, sample-size justification, or interim-analysis plan.
The listed serious-event terms are accompanied by percentages, but this summary does not include their event counts or detailed context. The event definitions do not establish causality, and the record does not provide comparative evidence that would separate treatment effects from disease-related or other causes. These limitations constrain both the precision and the interpretation of the reported safety experience.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System — NCT03643562.
- Registry record last updated 2024-01-17; status last verified 2023-12.
- Results first posted 2024-01-17.
- 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 describes NCT03643562, an open-label, single-group Phase 3 study of adrabetadex in participants with Niemann-Pick Type C disease and neurologic manifestations. It lists enrollment of 27, a start date of 2018-06-18, primary completion on 2021-11-02, and status as terminated. The reason for termination is not reported in the registry record.
Adrabetadex was administered by intrathecal injection every 2 weeks. The primary outcome counts participants with treatment-emergent adverse events and serious adverse events from baseline up to Week 134. The registry reports safety counts for treatment-naive and previously treated categories, and lists 0 deaths in each. It also lists 1 outcome measure and 0 analyses.
The categories are not randomized control groups, and the registry cautions that they are not like-for-like comparisons. The posted information is descriptive; inferential analyses, missing-data methods, and the reason for termination are not reported in the registry record.