Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB) (NCT02324049), a na phase 1, phase 2 study. The primary outcome is Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase I/II, open-label, single-group study of intravenous SBC-103 in MPS IIIB. The registry lists enrollment of 11 participants and a completed study. The study start date was 2015-01-22, and primary completion was 2017-10-16. No masking was used. Allocation is listed as not applicable, consistent with the absence of a randomized comparison group.

The treatment description identifies an initial-therapy period in Part A. Participants received one of three stated dosages, administered every other week for 24 weeks, then had a treatment break of at least 4 weeks. Enrollment began at the lowest dosage. In Part B, participants were to escalate to the next highest dose considered safe, with the listed options of 1.0 or 3.0 mg/kg every other week. The Part B description is incomplete in the registry record, so additional details of dose escalation or later treatment cannot be established from that description.

The primary outcome timeframe is baseline to Week 142. The registry’s endpoint description says severe TEAEs were summarized cumulatively over the entire study and separately for Part C, while all severe TEAEs over the entire study are presented. Details of Part C treatment are not reported in the registry record. The study summary describes its purpose as evaluating safety and tolerability, while its title also refers to pharmacokinetics and pharmacodynamics/efficacy.

A single-group open-label design can describe events observed during treatment, but it does not estimate a randomized treatment contrast. Without a concurrent control group, the study cannot separate events occurring during treatment from events that might also occur in the absence of the study drug. The registry record does not report a statistical analysis plan or a sample-size justification.

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.

Part A

Part B

Part C

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all participants for whom informed consent had been obtained, who had a confirmed diagnosis of MPS IIIB, and who had received any amount of SBC-103.

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: Safety Population: all participants for whom informed consent had been obtained, who had a confirmed diagnosis of MPS IIIB, and who had received any amount of SBC-103.

6. Primary Endpoint

The registry lists the primary outcome as Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs), measured over Baseline to Week 142.

The primary endpoint is the number of participants who experienced severe treatment-emergent adverse events (TEAEs) from baseline to Week 142. A TEAE is an adverse event that occurred after administration of the first study-drug dose on Day 1 of Part A. The endpoint therefore counts participants with at least one event meeting the stated severity definition, rather than counting every event as a separate participant outcome.

Severity was defined as incapacitating and requiring medical intervention. This is a specific threshold: it is not the same as seriousness, which is a separate adverse-event classification. An event can be serious without meeting the stated severity definition, and the registry information does not establish that every serious event was severe. Likewise, a count of participants with any other adverse event does not identify how many met the severe-TEAE definition.

A participant count is useful for describing how many people in the safety population experienced the defined outcome during the stated observation period. The endpoint description says the severe events were summarized cumulatively over the study, and separately for Part C, while all severe TEAEs across the entire study are presented. The primary endpoint count itself is not reported in the registry record. The serious-event counts posted separately do not fill that gap and should be interpreted as a different safety summary.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

The primary outcome is a binary participant-level measure: each participant either experienced a severe TEAE meeting the definition during the specified period or did not. Reporting the number of participants with the event describes the observed burden in the study population. It is distinct from an event count, because one participant can experience more than one event while still contributing once to a participant-level count.

The registry record defines the safety population as participants who had given informed consent, had a confirmed MPS IIIB diagnosis, and had received any amount of SBC-103. This is the population to which the safety endpoint refers. It is not necessarily interchangeable with every population used for pharmacokinetic or pharmacodynamic analyses; those analysis populations are not reported in the registry record.

How should an event definition be applied?

The endpoint combines timing and severity criteria. An adverse event qualifies as treatment-emergent if it occurred after the first study-drug dose on Day 1 of Part A. It qualifies as severe under the registry definition if it was incapacitating and required medical intervention. Applying both criteria consistently matters: counting all adverse events, all serious adverse events, or events that occurred before treatment would not measure the stated endpoint.

General statistical principle: a clearly defined event threshold makes a count interpretable, but it does not make different event classifications equivalent. Seriousness and severity describe different attributes. A serious-event summary is therefore not a proxy for a severe-TEAE endpoint unless the registry explicitly reports that the same events meet both definitions. It does not do so in the posted information.

What can a single-group design estimate?

The study’s single-group design supports a description of events observed among participants who received SBC-103. It does not provide a randomized contrast between treatment and control. A comparison with an external population would require assumptions about comparability that are not established in the registry record. No such analysis is reported.

General statistical principle: a confidence interval expresses uncertainty around an estimate under the assumptions of the method used. An interval around a participant count or event proportion could communicate sampling uncertainty, but it would not correct the lack of a comparator or establish causality. Confidence intervals for the primary safety outcome are not reported in the registry record.

What do the planning assumptions mean?

The sample-size assumptions associated with the posted planning illustrations describe a hypothetical two-arm calculation: two-sided significance level 0.05, equal allocation, a normal approximation, and an effect specified as a fraction of the observed effect. Those assumptions are not the study’s design, which is single-group, and the registry record does not identify them as the protocol’s original planning rationale. Any resulting sample sizes are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect.

General statistical principle: planning calculations depend on the target effect, variability, significance threshold, allocation, and analysis method. Changing those assumptions changes the planning result. An effect based on the observed result can be optimistic or unstable, particularly in a small study, and it should not be interpreted as independent confirmation of the observed result. The registry record does not report a sample-size justification for the trial itself.

The planning notes distinguish calculations for time-to-event outcomes, which use a total number of events under the stated method, from other calculations, which express participants per arm. The primary endpoint in this study is a participant count for a binary adverse-event outcome, not a reported time-to-event endpoint. The registry does not report a time-to-event analysis for the primary outcome.

Why can over-dispersion matter?

General statistical principle: over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, its uncertainty estimates can be too narrow and its tests can appear more decisive than warranted. The registry record does not report a model for the primary outcome or an assessment of over-dispersion, so no conclusion about its presence or treatment can be drawn.

What analysis is documented?

The registry lists one outcome measure and does not report an analysis for it. No inferential result, adjusted estimate, confidence interval, or hypothesis test for the severe-TEAE endpoint is reported in the registry record. The descriptive serious-event counts can be read as posted safety information, but they should not be mistaken for a complete statistical analysis of the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure: the number of participants who experienced severe TEAEs. It does not report an analysis of that outcome. Although the endpoint description says severe events were summarized cumulatively over the study and separately for Part C, the statistical handling of those summaries is not reported in the registry record.

Multiplicity arises when several outcomes, time periods, groups, or statistical tests are examined. General statistical principle: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis accounts for the multiple testing. The registry record does not describe a multiplicity adjustment, a hierarchy among outcomes, or a prespecified testing strategy. With no reported inferential analyses, it is not possible to determine whether or how multiplicity was handled.

Missing-data methods, participant discontinuations, and the amount of missing outcome information are not reported in the registry record. The safety-population definition identifies who was eligible for the safety summary, but it does not explain how missing follow-up or incomplete adverse-event collection was handled. The primary endpoint timeframe extends from baseline to Week 142, and the registry record does not state how participants with shorter observation were treated in the primary summary.

The record does not report a separate intention-to-treat analysis population or a detailed population definition for other study objectives. Consequently, the safety population should not be assumed to be the analysis population for every outcome. The limitations in reporting make it difficult to assess completeness, the handling of repeated observations, or the influence of missing information on the posted results.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bacteraemia (9.1%), pneumonia (9.1%), staphylococcal bacteraemia (9.1%), urticaria (9.1%), swelling face (9.1%).

The serious-adverse-event summary lists 3 affected participants among 11 at risk. The other-adverse-event summary lists 11 affected among 11 at risk, and the deaths entry is 0. These are participant counts in the posted safety summary, not treatment-versus-control comparisons. No control group was included in this study.

The listed serious-event terms are Bacteraemia, Pneumonia, Staphylococcal bacteraemia, Urticaria, Swelling face, and Flushing, each reported at 9.1%. The registry record does not provide enough information in this summary to determine how terms overlap within participants or to interpret the entries as causal effects. They should be read as reported event terms, not as evidence that SBC-103 caused each event.

Serious adverse events are not identical to severe TEAEs. The primary endpoint defines severe events as incapacitating and requiring medical intervention, while the separate safety summary reports serious events. The registry record does not report the primary severe-TEAE count, so the serious-event counts cannot stand in for that endpoint. The counts are descriptive and have no accompanying interval estimates in the posted information.

12. What the Result Does, and Does Not, Mean

The registry record describes a completed, open-label study of SBC-103 in 11 participants with MPS IIIB. It posts counts for serious and other adverse events, including 3 participants affected by serious events among 11 at risk, 11 affected by other events among 11 at risk, and 0 deaths. It also names serious-event terms and gives each listed term as 9.1%.

Those observations are safety descriptions from a single-group study. They do not establish what would have happened to similar participants without SBC-103, and they do not by themselves show that the treatment caused any listed event. The absence of a randomized comparator prevents a direct treatment-control estimate. The small enrollment also means the observed counts describe this study population and should not be read as a precise estimate for a broader population.

The primary outcome concerns severe TEAEs, defined as incapacitating events requiring medical intervention. Its result is not reported in the registry record. Serious adverse events and severe TEAEs are distinct categories, so the posted serious-event counts do not answer the primary question. Nor does the count of other adverse events show how many met the severity threshold.

The study title refers to safety, pharmacokinetics, and pharmacodynamics/efficacy, but the information available for this analysis does not report results for pharmacokinetic or pharmacodynamic/efficacy outcomes. No conclusion about those objectives can be drawn from the posted safety counts. Overall, the record supports a description of adverse events recorded during the study; it does not provide a controlled estimate of treatment effect, a complete account of the primary endpoint result, or evidence that the findings apply beyond the enrolled participants.

13. Why This Trial Matters Statistically

This study illustrates why a registry result needs to be interpreted in relation to its design and the exact outcome definition. A safety count can be informative about events recorded among treated participants, but it does not answer the same question as a randomized comparison. With a single group and no masking, the findings are descriptive and do not separate treatment-related effects from other explanations for events.

It also illustrates the importance of distinguishing severity from seriousness. The primary outcome defines severe TEAEs through incapacitation and the need for medical intervention. The separately posted adverse-event summary reports serious events and other events. Treating these categories as interchangeable would alter the question being answered. The primary severe-event count is not reported in the registry record, which limits interpretation of the named primary endpoint despite the presence of other safety counts.

Small studies can contribute useful early safety observations, especially when the study is designed to evaluate safety and tolerability. At the same time, a small enrollment makes descriptive counts sensitive to the experience of individual participants. Without uncertainty intervals or a comparator, readers should avoid turning the counts into strong claims about frequency, causation, or relative risk.

The record also demonstrates why design and analysis plans matter when reading planning calculations. A hypothetical two-arm sample-size illustration is not a description of a single-group trial’s achieved statistical power. Planning assumptions are not a substitute for a protocol’s justification, and the registry record does not report that justification. Keeping the trial’s actual design separate from generic planning illustrations helps prevent a calculation from being mistaken for evidence of effectiveness or safety relative to another treatment.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation is the absence of a concurrent comparison group. The study is recorded as single-group, open-label, and not masked. The observed adverse-event counts therefore cannot estimate a randomized difference or establish that an event was caused by SBC-103. There is no like-for-like control comparison in the registry record.

Enrollment was 11, which limits how much can be learned from the observed event counts about less common outcomes or the range of possible event frequencies. The record does not provide confidence intervals for the posted safety counts, so statistical precision is not quantified. The listed serious-event percentages should not be mistaken for a comparative effect estimate.

The registry record does not report the primary severe-TEAE outcome count, despite defining that endpoint and its timeframe as baseline to Week 142. The separate serious-event summary cannot replace it because seriousness and severity are different classifications. The study title refers to pharmacokinetics and pharmacodynamics/efficacy, but corresponding results are not included in the registry record for this analysis.

Further limitations concern reporting. The statistical analysis plan, sample-size justification, handling of missing data, participant-level follow-up completeness, and multiplicity strategy are not reported in the registry record. The treatment description for Part B is incomplete, and details of Part C are not reported. These omissions prevent a fuller assessment of treatment exposure, analysis choices, and the context for the endpoint summaries. The posted results should therefore be interpreted as limited descriptive safety information, not as a complete evaluation of all study objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB) — NCT02324049.
• Registry record last updated 2018-08-21; status last verified 2018-07.
• Results first posted 2018-07-12.
• 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.

18. Record Summary

NCT02324049 is a completed Phase I/II open-label, single-group study of intravenous SBC-103 in MPS IIIB. Enrollment was 11. The study started on 2015-01-22, and primary completion was 2017-10-16. Part A included 0.3, 1.0, or 3.0 mg/kg every other week for 24 weeks, followed by a treatment break of at least 4 weeks. The registry describes dose escalation in Part B but does not include the full description.

The primary endpoint was the number of participants with severe TEAEs from baseline to Week 142. Its result is not reported in the registry record. The separate safety summary lists 3 participants affected by serious adverse events among 11 at risk, 11 affected by other adverse events among 11 at risk, and 0 deaths. No randomized control comparison or statistical analysis of the primary endpoint is reported in the registry record.