A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously (NCT02618512), a na phase 1, phase 2 study. The primary outcome is Safety and Tolerability of SBC-103.

2. Clinical Question

The clinical question concerns the safety and tolerability of intravenous SBC-103 in people with mucopolysaccharidosis III, type B (MPS IIIB, also called Sanfilippo B) who had previously participated in the NGLU-CL01 study and had not previously received SBC-103. The registry describes NGLU-CL01 as a non-interventional study assessing structural brain abnormalities and blood-brain-barrier integrity using MRI and the cerebrospinal fluid/serum albumin index.

The study was open label and used a single-group design. It therefore asked how participants experienced treatment and what safety findings were observed during administration of SBC-103; it did not assign participants to a separate control treatment. The primary endpoint was safety and tolerability, assessed through treatment-emergent adverse events, including serious adverse events, infusion-associated reactions, antidrug antibodies, clinical laboratory tests, cerebrospinal fluid findings, vital signs, and prior and concomitant medications.

The registry reports three enrolled participants. Its primary-endpoint timeframe was planned from baseline to 164 weeks, while the actual timeframe was 96 weeks because the study terminated early. These details define the scope of the question: the record documents a small, uncontrolled safety study with a shorter actual observation period than planned. It does not establish how the findings compare with another treatment or with an untreated group.

3. Trial Design

This was an open-label Phase I/II study of SBC-103, administered intravenously to participants with MPS IIIB. The registry describes a single-group model, with no masking and no randomized allocation. Three participants were enrolled. The sponsor was Alexion Pharmaceuticals, Inc. The study began on 2015-10-15, and primary completion was recorded as 2017-08-18. Its status is terminated.

Participants were previously studied in NGLU-CL01 and had not previously received SBC-103. The SBC-103 arm description states that treatment began at 1 mg/kg by intravenous infusion once every other week for at least 12 weeks. After an evaluation of safety, tolerability, and pharmacodynamic data for each participant at 12 weeks, the dose was increased to 3 mg/kg once every other week. The record also states that infusions were to be at least 10 days apart. The remaining arm-description text is incomplete, so further administration details are not reported in the registry record.

The study had a safety and tolerability primary endpoint. The planned observation timeframe was baseline to 164 weeks, but the actual timeframe was 96 weeks because of early termination. The reason for termination is not reported in the registry record. The registry lists one outcome measure and zero analyses.

The design is important when interpreting the findings. An open-label, single-group study can describe what was observed among participants receiving the study drug, but the record does not supply a randomized control group for comparison. Its small enrollment also means that the reported counts describe only the participants in this study; they should not be read as precise estimates of how frequently events would occur in a broader population. No allocation concealment or masking comparison is described, and there is no basis in the record for treating the study as a comparative efficacy trial.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of SBC-103, measured over Planned duration was baseline to 164 weeks but due to early termination of the study, actual is 96 weeks..

The planned primary endpoint was safety and tolerability of SBC-103 in participants with MPS IIIB. The registry defines the central measure as the number of participants with treatment-emergent adverse events, including serious adverse events. It also lists infusion-associated reactions, antidrug antibodies, clinical laboratory tests, cerebrospinal fluid findings, vital signs, and prior and concomitant medications as components of the safety assessment.

Safety endpoints are used in clinical studies to record unwanted events and clinically monitored findings during exposure to an intervention. Counting participants with events gives a direct description of how many enrolled participants were affected, while the accompanying clinical assessments can provide context about the nature of findings observed during follow-up. These measures are descriptive in this single-group record; without a separate comparison group, they do not by themselves establish whether an event was caused by treatment or whether its frequency differs from another setting.

The planned timeframe ran from baseline to 164 weeks. The actual timeframe was 96 weeks because the study terminated early. The record does not report detailed endpoint results for every component named in the endpoint description. Consequently, the available summary should not be interpreted as a complete account of all laboratory, cerebrospinal fluid, vital-sign, antibody, medication, and infusion-reaction data collected or assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be interpreted in light of the study question and design. This study was open label and single group, with three enrolled participants. Its primary endpoint concerned safety and tolerability rather than a stated comparison between randomized treatment groups. The registry lists zero analyses, so an inferential statistical analysis plan or reported model is not available in the registry record.

What do the participant counts represent?

For a binary safety outcome, a participant is counted as having or not having the specified event under the definition used for that outcome. A count of participants with an event is a direct description of observed participants. It is not the same as a count of every event: one participant could have more than one event, and an event-term list can represent multiple recorded terms. The registry reports the serious and other adverse-event participant counts separately, along with the listed serious-event terms. The record does not provide detailed event-level data in this summary to reconcile terms, timing, or recurrence.

Participant counts are especially straightforward to communicate in a small study, but they have limited precision as estimates of what might happen in a wider population. When only a few participants are observed, the experience of an individual participant can substantially influence the overall description. General statistical principle: uncertainty intervals can help show the range of population values compatible with observed data, but no confidence interval for these safety counts is reported in the registry record. Such an interval would not remove the limitations arising from the small enrollment or the lack of a control group.

What does an open-label, single-group design allow?

A single-group study can record events observed during treatment and describe how participants were monitored. It cannot make the same direct between-group comparison as a study with a concurrent control group. Because the study was open label, participants and investigators knew that SBC-103 was being administered. This design does not by itself determine whether a recorded event was caused by treatment. A causal comparison would require information and a design that distinguish treatment exposure from other possible explanations; such a comparison is not reported in the registry record.

The absence of a comparative group also means that a treatment contrast, such as a difference in event rates between groups, is not available from this design. The registry's counts should therefore be read as observations in the SBC-103 group rather than as comparative effects. There is no reported randomized allocation, masked assessment, or analysis adjusting for other factors in the registry record.

How should the planning illustrations be read?

Any sample-size illustrations associated with posted results are planning illustrations, not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is used; other illustrations are expressed as participants per arm. These assumptions describe a hypothetical planning exercise and do not describe the actual single-group study, which had three enrolled participants.

General statistical principle: sample-size planning asks how many participants might be needed under chosen assumptions to detect a specified effect with a chosen probability. It does not measure the probability that a completed study's finding is true. In particular, a planning calculation based on an observed effect is sensitive to that effect estimate and should not be called observed power. The registry record does not report that these planning assumptions were the study's original design assumptions or that they informed its conduct.

Why do precision and over-dispersion matter generally?

General statistical principle: confidence intervals describe uncertainty around an estimate under the assumptions of a statistical method. For event counts, the width and meaning of an interval depend on the data structure and model. Over-dispersion occurs when variability in count data exceeds what a selected model assumes; ignoring it can make uncertainty appear smaller than it is. This trial's posted primary outcome is a participant count, and the registry record does not report a count model, an over-dispersion assessment, or a confidence interval. These concepts therefore offer general context, not a description of analyses performed for this study.

Overall, the available statistical information supports descriptive interpretation: the registry reports participant counts and event terms, but lists no analyses. It does not report hypothesis tests, adjusted estimates, confidence intervals, prespecified subgroup analyses, or a statistical model. Those omissions mean that the data should not be recast as evidence from an inferential or comparative analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("SBC-103")
n      <- c(3)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  SBC-103  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It does not report a multiplicity strategy, such as how statistical testing across multiple outcomes or repeated assessments would be controlled. Since no inferential analyses are listed, the record does not support a claim that a particular adjustment was or was not applied in an analysis beyond noting that the strategy is not reported in the registry record.

The primary endpoint description includes several safety domains: treatment-emergent adverse events, serious adverse events, infusion-associated reactions, antidrug antibodies, laboratory tests, cerebrospinal fluid findings, vital signs, and medication history. The record does not specify the detailed analysis population or how each domain was summarized. It also does not report a participant-level accounting of missing observations, reasons for missingness, or a method for handling missing data. The actual primary-endpoint timeframe was 96 weeks rather than the planned baseline-to-164-week timeframe because the study terminated early; participant-specific follow-up information is not reported in the registry record.

Analysis populations are not described in the registry record. In particular, the record does not state whether all enrolled participants were included in every safety summary, how exposure was defined for analysis, or whether any participants were excluded from particular assessments. With three participants enrolled, these omissions matter for understanding precisely which observations contribute to each reported count. The posted participant counts remain descriptive, but interpretation of completeness and follow-up cannot be made more specific without those details.

12. 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: device related infection (66.7%), wound dehiscence (33.3%), erythema multiforme (33.3%), catheter placement (33.3%).

The registry reports that serious adverse events affected 2 participants among 3 at risk in the SBC-103 group. Other adverse events affected 3 participants among 3 at risk, and deaths were recorded as 0. These are counts of participants, not necessarily counts of individual event episodes. A participant may have more than one adverse event, so the serious and other-event summaries should not be treated as mutually exclusive categories unless the registry defines them that way; that definition is not reported in the registry record.

The registry's listed serious adverse-event terms and percentages are Device Related Infection, 66.7%; Wound dehiscence, 33.3%; Erythema Multiforme, 33.3%; and Catheter placement, 33.3%. These are presented as registry-listed terms, not as a basis for calculating additional totals or comparisons. The record does not provide detailed information about event onset, duration, severity beyond the serious classification, recurrence, management, or the investigator's assessment of relatedness to treatment.

Serious adverse events are not synonymous with events caused by a study drug. The counts describe what was recorded in the study group; attribution and clinical context require information beyond the counts. Because there was no separate comparator group and the study enrolled three participants, these results cannot establish a relative risk or a population-level event rate with high precision.

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

The posted results document safety observations in a small group of participants receiving intravenous SBC-103. They report serious adverse events in 2 participants among 3 at risk, other adverse events in 3 participants among 3 at risk, and 0 deaths. They also identify several serious-event terms with registry-listed percentages. These are descriptive findings from the participants enrolled in this study.

The results do not establish that SBC-103 caused any particular event. Events recorded during a study can have different explanations, and the single-group design does not provide a separate group for comparison. The open-label design also means that treatment was not masked. The record does not report a causal analysis, an adjusted comparison, or inferential analyses that would quantify a treatment effect.

Nor do the findings provide a precise estimate for a broader population. Three participants were enrolled, and the primary-endpoint observation period was shorter than planned: actual follow-up was described as 96 weeks rather than the planned baseline-to-164-week duration because the study terminated early. The reason for early termination and participant-specific follow-up are not reported in the registry record. This limits conclusions about the duration and completeness of observation.

The record identifies the endpoint domains that were intended for safety and tolerability assessment, but it does not report detailed results for each listed domain. Therefore, the available summary should not be read as a complete account of all laboratory, cerebrospinal fluid, vital-sign, antibody, infusion-reaction, and medication findings. The registry also lists no analyses, so the reported counts should not be interpreted as statistically tested comparisons.

In general, an uncontrolled safety study can provide a record of events among exposed participants and may inform questions for further study. That general role does not convert these observations into proof of efficacy, proof of harm, or a comprehensive estimate of safety. The posted data support only a careful description of the reported participants and outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable because its structure and scale make the distinction between description and comparison especially important. It was an open-label, single-group study with three participants. Its registry record reports safety and tolerability as the primary endpoint, rather than a randomized comparison of treatment groups. The observed counts can be reported directly, but they cannot establish how outcomes would have differed under another treatment or without treatment.

The endpoint spans several types of information, from adverse events to laboratory findings, cerebrospinal fluid, vital signs, and antidrug antibodies. Such breadth can be important for characterizing safety, but it also makes complete reporting and clear definitions essential. The registry lists one outcome measure and zero analyses; detailed analysis methods, analysis populations, and results for each component are not reported in the registry record. That limits how fully readers can evaluate the endpoint as a whole.

The difference between planned and actual observation time also matters. The planned primary-endpoint timeframe extended from baseline to 164 weeks, while the actual timeframe was 96 weeks due to early termination. The registry does not give the reason for termination or participant-specific follow-up. Duration and completeness of follow-up are relevant when interpreting a safety record because the amount of observation affects which events can be recorded.

Finally, the data illustrate why small-study counts should remain tied to the people actually observed. The results are useful as a transparent description of the recorded study experience, but their statistical scope is limited. They do not supply a controlled estimate, a precise population rate, or a reported inferential analysis. Keeping those boundaries clear is central to interpreting early-phase safety evidence.

15. 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.

Several features specific to this study constrain interpretation. Enrollment was three participants, and the study used an open-label, single-group design. There was no separate control group, so the reported event counts cannot be used as a direct comparison with another treatment or with no treatment. The record does not report randomization, masking, or a causal analysis.

The study terminated early. The planned primary-endpoint timeframe was baseline to 164 weeks, while the actual timeframe was 96 weeks. The reason for early termination and the length of follow-up for each participant are not reported in the registry record. The difference between planned and actual observation limits the available context for interpreting event timing and duration.

The primary endpoint included multiple safety domains, but detailed results for all named components are not reported in the registry record. The registry lists one outcome measure and zero analyses. Statistical methods, analysis populations, missing-data handling, participant-level exposure details, and multiplicity procedures are not reported in the registry record. These omissions prevent a fuller assessment of how observations were organized and analyzed.

The adverse-event summary provides participant counts and selected serious-event terms with percentages, but it does not include detailed event narratives, timing, recurrence, or treatment-relatedness assessments in the information described. The counts therefore should not be treated as evidence that treatment caused an event. The incomplete arm-description text also means that administration details beyond those explicitly stated are not reported in the registry record.

These limitations do not erase the descriptive information that is reported, but they define its reach. The findings characterize the recorded experience of a very small group during the actual study timeframe; they do not provide a controlled estimate or a comprehensive safety profile.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously — NCT02618512.
• Registry record last updated 2018-04-17; status last verified 2018-03.
• Results first posted 2018-04-17.
• 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.

19. Record Summary

NCT02618512 is a Phase I/II open-label, single-group study of intravenous SBC-103 in previously studied, treatment-naïve participants with MPS IIIB who participated in NGLU-CL01. The registry lists Alexion Pharmaceuticals, Inc. as sponsor, three participants enrolled, and study status as terminated. The recorded start was 2015-10-15, and primary completion was 2017-08-18.

The primary endpoint was safety and tolerability, including treatment-emergent adverse events and other specified clinical assessments. The planned timeframe was baseline to 164 weeks; the actual timeframe was 96 weeks because of early termination. The registry reports serious adverse events affecting 2 participants among 3 at risk, other adverse events affecting 3 participants among 3 at risk, and 0 deaths. It lists one outcome measure and zero analyses. The record does not report a control-group comparison or the reason for termination.