A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum (NCT05569252), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b.

2. Clinical Question

The study asked whether DS-1211b could be evaluated for safety, tolerability, pharmacodynamics, and pharmacokinetics in individuals with pseudoxanthoma elasticum (PXE). Its primary outcome was the number of participants with treatment-emergent adverse events among those receiving DS-1211b. The registry also reports adverse-event counts for the dose groups and placebo. This is a safety question, not a direct test of whether the study treatment improves PXE or its symptoms.

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study of DS-1211b in individuals with PXE. The registry records enrollment of 65 participants. It lists three active-treatment groups—low, middle, and high dose—and a placebo group. Participants in each group were assigned a tablet once daily for 12 weeks. Dose amounts are not reported in the registry record.

The study began on 2022-10-20, had a primary completion date of 2023-11-21, and is listed as completed. The registry summary states that the study was designed to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics. The primary outcome concerns treatment-emergent adverse events in participants receiving DS-1211b. Secondary outcomes include pharmacokinetic measures: maximum concentration (Cmax), time to maximum concentration (Tmax), trough plasma concentration (Ctrough), and area under the plasma concentration-time curve (AUC).

Double blinding means that the study used masking, but the registry record does not specify which roles were masked or how masking was maintained. It also does not report the randomization procedure, planned allocation ratio, or dose amounts. Although the registry lists 65 enrolled participants, the reported group denominators for the safety results are 16 in each DS-1211b group and 17 in the placebo group. These are the denominators shown for the posted adverse-event counts; further participant-flow details are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treatment-emergent adverse events were assessed in the Safety Analysis Set.

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: Demographics and baseline characteristics were assessed in the Intent-to-Treat Analysis Set.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b, measured over From the date of signing informed consent form up to Day 98 (14 days after last dose of study drug) post-dose of 12-week treatment period.

The primary outcome is the number of participants with treatment-emergent adverse events (TEAEs) among participants receiving DS-1211b. The registry defines a TEAE as an event that begins on or after the first dose of study drug, or an event that began earlier and worsened after the first dose. Events were coded using MedDRA version 26.1. The stated observation period runs from signing informed consent through Day 98, described as 14 days after the last dose following the 12-week treatment period. The endpoint was assessed in the Safety Analysis Set.

A participant count is a binary outcome summarized as the number with an event among those assessed. It provides a direct description of how many participants experienced an event under the registry’s definition and observation period. It does not by itself establish that the study drug caused an event. Nor does a count describe how severe, persistent, or consequential an event was unless those characteristics are reported separately. The registry record identifies this as the primary outcome but does not report an inferential statistical method or an adjusted comparison for it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a safety endpoint based on counts of participants with events. The results are descriptive: they state how many participants in each group were recorded with serious and other adverse events, along with the group denominator. The record does not report a statistical test, confidence interval, p-value, or adjusted treatment-effect estimate for these results. The interpretation should therefore emphasize the observed counts and their uncertainty, rather than imply a formal comparison that is not reported.

What does a participant count represent?

For a binary outcome, each participant is classified according to whether the defined event occurred during the observation period. The numerator is the number of participants recorded with the event, and the denominator is the number assessed in that group. This presentation is easy to interpret in clinical context, but it does not capture every feature of adverse events. For example, a count alone does not describe how often an event recurred in the same participant, how long it lasted, or whether it led to a change in treatment. Such details are not reported in the primary outcome description.

The endpoint is based on TEAEs, which the registry defines by timing in relation to the first dose. An event can qualify if it begins after the first dose, or if it began earlier and worsened after that dose. This definition helps specify which events belong in the endpoint, but temporal eligibility does not prove that the study drug caused the event. Attribution and the method used to assess relatedness are not reported in the registry record.

Why keep the group denominators in view?

Counts are easier to compare when the number of participants assessed in each group is also considered. The posted safety denominators are 16 for each DS-1211b dose group and 17 for placebo. The counts should not be read without those denominators, because a given count has a different meaning when the number assessed differs. No new pooled total or between-group effect is calculated. The registry record does not provide an analysis that combines the dose groups or adjusts for any other factors.

General statistical principle: a confidence interval expresses the range of values compatible with the data under a specified statistical method and assumptions. It helps readers distinguish a precise estimate from one with substantial uncertainty. No confidence intervals are reported for these adverse-event results. With limited group sizes, the observed counts can provide only limited precision about event frequencies beyond the participants studied. In particular, observing no serious events in a group does not prove that such events cannot occur.

What can randomization and blinding contribute?

Random assignment is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. Double blinding is intended to reduce the influence of knowledge of assignment on participant or study-team behavior and assessment. These are general design principles, not evidence that all potential biases were eliminated in this study. The registry identifies the trial as randomized and double-blind but does not report sequence generation, concealment, who was masked, or procedures for evaluating whether masking was maintained.

The study has three DS-1211b dose groups and a placebo group. Results across several groups can raise questions about how comparisons were selected and how the chance of false-positive findings was handled. The registry record does not report a statistical analysis plan, a primary contrast among groups, or a multiplicity adjustment. It would therefore be inappropriate to infer a prespecified dose comparison or to claim that the posted counts demonstrate a dose trend.

How should planning calculations be distinguished from trial results?

Any sample-size illustrations associated with the results are planning exercises, not observed trial outcomes. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those assumptions describe the illustration; they are not reported as the design basis used for this trial. The registry record does not report the trial’s sample-size justification or the assumptions used to select enrollment. Planning calculations do not represent observed power and should not be used to claim that the trial was adequately powered for its safety outcome.

More generally, the meaning of an analysis depends on its endpoint definition, population, statistical model, and handling of incomplete data. The primary endpoint specifies the Safety Analysis Set, but further details about population construction, missing observations, or analysis methods are not reported in the registry record. Without those details, the posted counts are best treated as the registry’s descriptive safety results, not as a complete account of all analyses performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and identifies pharmacokinetic measures among the secondary outcomes, including Cmax, Tmax, Ctrough, and AUC. It does not report a statistical analysis plan explaining how these outcomes were prioritized, how many comparisons were planned, or whether multiplicity was addressed. When several outcomes or group comparisons are considered, the chance of at least one apparently notable result can increase. General statistical principle: methods for controlling multiplicity can help manage that issue, but no such method is reported in the registry record.

Missing-data methods are not reported in the registry record. The primary outcome specifies the Safety Analysis Set, but the record does not describe how participants with incomplete follow-up, missing event information, or other deviations were handled. The posted denominators indicate the participants represented in the group-level safety results; they do not, by themselves, explain participant flow or the handling of missing observations.

The registry record reports zero analyses in the analysis listing. It does not provide inferential results for the primary endpoint, such as a statistical test, confidence interval, or adjusted comparison. The analysis population is identified for the TEAE endpoint as the Safety Analysis Set, but other analysis populations and their definitions are not reported. The record also does not report interim analyses, stopping rules, a prespecified multiplicity strategy, or a statistical plan. These omissions limit assessment of how the recorded outcome results relate to the full analysis plan, if one existed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: circulatory collapse (6.2%).

The serious adverse-event counts are reported by group. The low-dose group had 1 participant with a serious adverse event among 16 at risk. The middle-dose group had 0 among 16, the high-dose group had 0 among 16, and placebo had 0 among 17. The registry reports 0 deaths in every group. These figures describe the posted safety results; they do not establish whether an event was caused by treatment.

The registry lists circulatory collapse as a top serious-event term with 6.2%. It does not report enough context alongside that entry to assign the term to a specific group or infer a participant count from the percentage. It should therefore be retained as a registry-listed term and percentage, without further interpretation.

Serious adverse events and other adverse events are separate categories in the posted results. The serious-event counts should not be confused with all TEAEs. The endpoint definition includes events based on their timing and worsening after the first dose, while seriousness is a separate classification. General statistical principle: few or no observed serious events in a group do not rule out the possibility of such events in a larger or different population. The record does not report confidence intervals or a formal between-group analysis for these figures.

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

The registry results describe adverse events recorded during a specified safety observation period in a randomized, double-blind, placebo-controlled study of DS-1211b in individuals with PXE. They show the reported numbers of participants with serious and other adverse events in each dose group and in placebo, and report no deaths in any group. This is useful descriptive information about the participants included in the safety results.

The counts do not establish that DS-1211b caused or prevented any event. They also do not show that the groups had equivalent safety profiles. A formal comparison, with its statistical method and uncertainty estimates, is not reported in the registry record. The small group denominators mean that the posted counts provide limited precision about event frequencies beyond the study participants. A group with no recorded serious events should not be interpreted as having no possibility of serious events.

The study was designed to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics. The primary endpoint concerns TEAEs; it is not a measure of PXE symptoms, visual function, cardiovascular outcomes, or quality of life. The registry record does not report a clinical-benefit endpoint or a result that would establish a treatment effect on those outcomes. The listed pharmacokinetic measures concern drug concentration and exposure, but their numerical results are not included in the registry record described for this analysis.

Interpretation is also limited by the absence of reported details about missing data, the analysis plan, multiplicity, and inferential comparisons. The outcome counts can be read as the registry’s descriptive account, but they cannot answer questions that require those additional details. The results should not be extended automatically to people outside the studied population or to treatment durations beyond the 12-week regimen and stated safety follow-up.

13. Why This Trial Matters Statistically

This study is statistically notable for presenting safety results across three DS-1211b dose groups and a placebo group in a randomized, double-blind Phase 2 design. The endpoint is clinically interpretable as a count of participants with treatment-emergent adverse events, and the registry gives group denominators as well as serious and other adverse-event counts. Keeping the denominators alongside the counts makes clear how much information underlies each group’s description.

At the same time, the results illustrate why descriptive counts and inferential conclusions are not interchangeable. Each group includes a limited number of participants, and the registry record does not report confidence intervals, p-values, or an adjusted comparison. The posted counts can describe what was observed, but they do not quantify how uncertain the underlying event frequencies are or determine whether differences among groups are statistically persuasive.

The three-dose structure also makes the analysis question important. A comparison of each dose with placebo, a trend across dose groups, and a pooled active-treatment comparison are different questions. The registry record does not identify which of these was prespecified or report a method for addressing multiple comparisons. Without that information, the group counts should not be used to infer a dose-response relationship.

The record also illustrates the importance of distinguishing the intended study purpose from the outcome actually described. The study aimed to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics, while the primary outcome is an adverse-event count. That count does not answer every question about PXE or clinical benefit. Transparent reporting of populations, analysis methods, missing-data handling, and uncertainty would be needed for a fuller statistical assessment.

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 registry record does not report the actual amounts of DS-1211b used in the low-, middle-, and high-dose groups. It also does not provide detailed eligibility criteria, the randomization method, allocation concealment, the roles that were masked, or how masking was maintained. These details would help readers assess how the groups were formed and how the study was conducted.

The safety results include group denominators and counts, but the registry record does not report confidence intervals, p-values, adjusted estimates, or a statistical comparison for the primary outcome. It does not state whether the three active-treatment groups were compared separately with placebo, combined, or assessed using another planned contrast. The statistical analysis plan, multiplicity approach, sample-size justification, and interim-analysis procedures are not reported in the registry record.

The record identifies the Safety Analysis Set for the TEAE assessment but does not explain the set’s construction, provide participant-flow details, or describe how missing event information or incomplete follow-up was handled. The serious-event term circulatory collapse is listed with 6.2%, but the accompanying context does not support assigning it to a group or interpreting it as a count. The record also does not provide detailed event-level information such as duration or outcome for the adverse events.

Finally, the reported study regimen lasted 12 weeks, with the stated safety observation period extending through Day 98. The registry results therefore describe the safety information collected under that study context; they do not establish what might occur with longer treatment or in populations not represented in the study. The registry’s descriptive counts should be interpreted within these reporting limits.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum — NCT05569252.
• Registry record last updated 2024-12-31; status last verified 2024-12.
• Results first posted 2024-12-31.
• 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

This completed Phase 2 study evaluated DS-1211b in individuals with PXE. It was randomized, double-blind, placebo-controlled, and parallel-group, with 65 participants enrolled. Participants received a low, middle, or high dose of DS-1211b, or placebo, once daily for 12 weeks. The registry identifies safety, tolerability, pharmacodynamics, and pharmacokinetics as study aims.

The primary outcome was the number of participants with TEAEs in the Safety Analysis Set. The posted safety results report serious and other adverse-event counts by group, with no deaths reported. The registry also lists pharmacokinetic secondary outcomes. It does not report inferential comparisons, confidence intervals, a statistical analysis plan, missing-data methods, or a sample-size justification. The event counts are descriptive and should not be interpreted as proof of causation or as evidence of clinical benefit.