Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study (NCT03563053), a na phase 3 study. The primary outcome is Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study.

2. Clinical Question

The primary objective was to monitor and evaluate long-term safety and tolerability. Secondary and exploratory objectives concerned health-related quality of life and central nervous system symptoms. Quality of life was assessed using the EQ-5D-5L scale. Neurological symptoms were assessed using the modified International Cooperative Ataxia Rating Scale, or mICARS, and Clinical Global Impression measures of severity and change.

This is an extension study among people who had taken part in an earlier study, not a comparison of EryDex with a control treatment. Its results can describe safety events and changes measured during follow-up in this study population. Without a concurrent control group, the design cannot isolate treatment effects from changes over time, the course of the condition, or other influences. The registry record does not report numerical results for the listed quality-of-life or neurological symptom outcomes.

3. Trial Design

This was a Phase 3, open-label, single-group extension study of the EryDex System in patients with ataxia telangiectasia who participated in the ATTeST-IEDAT-02-2015 study. The registry lists an enrollment of 104 and identifies Quince Therapeutics S.p.A. as the sponsor. The study started on 2018-06-12, had a primary completion date of 2022-09-02, and is listed as terminated. The reason for termination is not reported in the registry record.

Allocation is listed as not applicable, masking as none, and the model as single group. These features mean that the registry does not describe randomized assignment to distinct treatment groups or blinding of participants and investigators. The study therefore provides observations during extension treatment, rather than a randomized estimate contrasting EryDex with another intervention or usual care.

The intervention was the EryDex System, described as delivering approximately 14-22 mg of dexamethasone sodium phosphate. Treatment was planned for 12 months, and could continue beyond that period until a participant withdrew consent or the investigator decided to stop treatment following a risk-benefit assessment. The primary safety timeframe is described as extending from baseline through follow-up, approximately 60 days after the last infusion, with the stated maximum duration of up to 50.5 months. The registry also describes follow-up through 30 days after the final visit or at least 60 days after the final infusion, whichever was longer.

Long-term safety and tolerability were the primary objective. The secondary objective was to evaluate long-term change in health-related quality of life using EQ-5D-5L. Exploratory objectives concerned mICARS and Clinical Global Impression severity and change. The protocol details beyond these descriptions, including a statistical analysis plan, 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: Safety Population (SAF): the Safety Analysis Set consisted of all patients who provided informed consent or assent and who received any dose of study medication during IEDAT-03-2018 study. The Safety Analysis Set was used for all safety analyses.

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: In this trial, the Total or Overall Set (N=104) numerically corresponds to the Safety set, which included all patients who provided informed consent or assent and who received any dose of study medication during ATTeST-IEDAT-03-2018 study (i.e., "Date performed" given on the "EDS-EP Infusion" eCRF page at any Visit).

6. Primary Endpoint

The registry lists the primary outcome as Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study, measured over From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months).

The primary outcome concerns the number of treatment-emergent adverse events, treatment-emergent serious adverse events and adverse events of special interest recorded throughout the study. The stated timeframe begins at baseline and continues through follow-up, described as approximately 60 days after the last infusion and up to 50.5 months. The endpoint description says adverse events were assessed from signing informed consent at baseline through the final study visit, with additional follow-up after that visit or after the final infusion.

Safety endpoints are used to document unwanted medical events occurring during treatment and follow-up. Recording serious events separately helps distinguish events classified as serious from the broader set of adverse events; adverse events of special interest are also tracked as a distinct category. These counts can describe the safety experience observed among participants in the study. They do not, by themselves, establish that treatment caused an event. Events may occur for reasons unrelated to treatment, and a single participant may experience more than one event.

The registry record defines the safety analysis set as participants who provided informed consent or assent and received any dose of study medication in this study. The posted safety summary reports 104 participants at risk for serious events and 104 at risk for other events, with 12 recorded as affected by serious events and 98 by other events. It also records 0 deaths. These participant counts are not necessarily identical to the total number of events, and the registry’s primary outcome is worded as a number of events. A complete event-level account and numerical results for adverse events of special interest are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, open-label extension and lists no analysis records. This means the posted information supports descriptive interpretation of the reported safety counts and event terms, but it does not document a comparative statistical analysis. The methods and concepts below explain how such results are generally understood; they do not assert that any particular method was used in this study unless stated in the registry record.

What does a single-group design tell us?

In general, a single-group study follows participants receiving an intervention and records outcomes over time. It can show what was observed in that group, including adverse events during the observation period. A concurrent comparator is often used to help distinguish changes associated with an intervention from background changes, other care, or the natural course of a condition. This study has no concurrent comparator listed, so its counts are descriptive and cannot estimate a treatment-versus-control contrast.

Open-label means that masking is listed as none. In general, when participants and study personnel know the treatment being received, expectations or awareness may influence reports, clinical assessments, follow-up, or event classification. This does not show that any such influence occurred in this study. It is a design consideration when interpreting subjective measures, including quality-of-life questionnaires and clinical global impressions.

What do event counts represent?

An adverse-event count and a count of participants with an adverse event answer different questions. One participant can experience multiple events, so the total number of events can exceed the number of affected participants. The posted safety summary gives 12 participants affected by serious adverse events and 98 affected by other adverse events, while the primary outcome is described as a number of events. Those participant counts should not be treated as event totals. The registry record does not provide a complete event-level breakdown in the summary available for interpretation.

Seriousness is a classification of an adverse event, not a judgment that the event was caused by treatment. In general, adverse events are recorded during a specified period and may be assessed for seriousness and possible relationship to the intervention. The registry identifies serious events and adverse events of special interest as outcome categories, but detailed rules for event classification and attribution are not reported in the registry record. The listed serious-event terms and percentages therefore describe the reported summaries, rather than proving cause.

Why does the follow-up period matter?

Safety counts depend on how long participants are observed and whether follow-up is complete. Longer observation creates more opportunity to record events, while early discontinuation may shorten an individual participant’s exposure or follow-up. The registry describes treatment for 12 months with possible extension, and a follow-up period tied to the final visit or last infusion. It also gives a timeframe of up to 50.5 months. These descriptions clarify that observation could extend beyond the initial treatment period, but the registry record does not report participant-level follow-up duration or exposure time for the safety summaries.

In general, rates that account for time at risk can aid comparisons when observation time varies, whereas simple counts do not account for that variation. No person-time rate or exposure-adjusted safety analysis is reported in the registry record. The posted participant counts therefore should not be interpreted as rates per unit of time.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified model and analysis. It can show a range of values compatible with the data and assumptions, rather than only a single point estimate. No confidence intervals for the safety results are reported in the registry record. In this single-group setting, an interval around an event frequency would not resolve the absence of a comparator or establish that treatment caused an event.

What analyses are documented?

The registry lists zero analyses. It names the safety analysis population as those who provided informed consent or assent and received any dose of study medication in this study. Beyond that definition, the statistical analysis plan, outcome-specific analysis methods, handling of repeated measurements, and methods for missing observations are not reported in the registry record. The listed objectives and outcome measures describe what the study intended to assess, but they do not by themselves specify the statistical procedures used to analyze results.

More generally, repeated assessments such as EQ-5D-5L, mICARS, and Clinical Global Impression measures can require methods that account for multiple visits and incomplete follow-up. The choice depends on the measurement schedule, data structure, estimand, and assumptions about missingness. None of those analytical details should be inferred from the names of the measures or the planned timepoints alone. Numerical results for the listed quality-of-life and neurological outcomes are not reported in the registry record.

How should results be compared?

General comparisons across studies can be misleading when populations, follow-up periods, event definitions, and data collection differ. This extension study’s population, treatment duration, and follow-up structure are specific to its design. Comparisons with other studies would require aligned definitions and careful accounting for those differences; such comparative analyses are not reported in the registry record. The appropriate interpretation of the posted safety counts is therefore confined to what was recorded in this study, without treating the counts as evidence of a causal effect or as a controlled comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety objective, a secondary quality-of-life objective, and exploratory objectives involving neurological symptoms and Clinical Global Impression assessments. Several outcomes are named, including changes in EQ-5D-5L and mICARS scores and clinical global assessments at specified timepoints. When a study evaluates multiple outcomes, multiplicity is a general statistical concern: the more hypotheses assessed, the greater the chance that some results may appear notable by chance if each is interpreted independently. Methods to address this depend on the prespecified analysis plan and the inferential claims intended.

Any multiplicity strategy, such as a hierarchy of outcomes or adjustment of significance thresholds, is not reported in the registry record. The record lists zero analyses, and it does not report numerical results for the secondary or exploratory outcomes. Therefore, no claim about adjustment, statistical significance, or prioritization among those outcomes can be made from the registry information described.

Missing-data methods are also not reported in the registry record. In general, missing measurements can affect interpretation when participants discontinue, miss visits, or have outcomes that are not collected. Assumptions about why measurements are missing and the approach to incomplete follow-up can influence longitudinal estimates. The treatment description allows treatment to stop following consent withdrawal or an investigator’s risk-benefit decision, but it does not explain how any resulting missing outcome measurements were handled statistically.

The safety population is defined as participants who provided informed consent or assent and received any dose of study medication. The record does not report additional analysis populations for the quality-of-life or neurological outcomes, or whether the same participants contributed data at every visit. Interim analyses and stopping rules are not reported in the registry record. The study status is listed as terminated, but the reason for termination is not reported; no reason or analytical consequence should be inferred from that status alone.

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: forearm fracture (1.9%), lower respiratory tract infection (1.0%), pneumonia (1.0%), viral infection (1.0%), b-cell limphoma (1.0%).

The safety summary records 12 of 104 participants as affected by serious adverse events and 98 of 104 as affected by other adverse events. It records 0 deaths. These are participant counts, not necessarily the total numbers of distinct events: one participant can have more than one event. The primary outcome is described as a number of events, so the participant counts should not be substituted for an event total.

The listed serious-event terms are forearm fracture at 1.9%, lower respiratory tract infection at 1.0%, pneumonia at 1.0%, viral infection at 1.0%, B-Cell limphoma at 1.0%, and Hodgkin's Disease at 1.0%. The registry record does not report detailed event-level counts for these terms in the available summary, nor does it state whether each term represents one participant, multiple events, or both. These percentages should be read as the registry’s reported values, not recalculated from the participant counts.

In general, an adverse event occurring during a study is not, by itself, evidence that the intervention caused it. The open-label, single-group design has no concurrent comparison group to provide a direct contrast. The registry record also does not report detailed assessments of relatedness, timing, duration, or outcomes for the listed events. The figures describe safety observations in this study population and should not be interpreted as a controlled estimate of treatment-attributable risk.

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

The registry record documents an extension study designed primarily to monitor long-term safety and tolerability of the EryDex System among participants with ataxia telangiectasia who had taken part in an earlier study. The safety population included 104 participants. The posted summary records serious adverse events affecting 12 participants, other adverse events affecting 98 participants, and 0 deaths. It also lists selected serious adverse event terms with their reported percentages.

These findings describe what was recorded during the study’s treatment and follow-up period. They do not show how the event experience would compare with a control group, because the study is single-group and open-label. The results do not establish that EryDex caused the reported events, nor do they establish that the events would have occurred in the absence of treatment. The event counts are not a direct measure of treatment benefit, and the registry record does not report numerical results for the listed quality-of-life or neurological outcomes.

The study intended to evaluate quality of life using EQ-5D-5L and neurological symptoms using mICARS and Clinical Global Impression measures. Those objectives indicate areas the investigators planned to assess, but objective descriptions alone are not outcome results. The registry record does not report their numerical findings or the statistical methods used to analyze them. It is therefore not possible from the posted information to assess the direction, magnitude, or precision of change on those measures.

The listed safety counts should also be interpreted in relation to the study’s duration and follow-up. Treatment could continue beyond the planned 12-month period, and the safety timeframe extended through follow-up after the final infusion. Individual follow-up duration and exposure-adjusted analyses are not reported in the registry record. Overall, the findings are descriptive observations from this extension-study population; they do not provide a controlled estimate of efficacy or treatment-attributable safety risk.

13. Why This Trial Matters Statistically

This study illustrates a common statistical distinction between describing outcomes and estimating a treatment effect. A single-group extension can collect long-term safety observations in people who continue from an earlier study. Such follow-up may add information about events recorded during continued treatment and subsequent observation. But without a concurrent comparator, the design cannot separate treatment-related effects from background events, changes in the underlying condition, or other influences.

The extension structure also makes the population important. Participants had taken part in the ATTeST-IEDAT-02-2015 study, so the registry findings concern this group of continuing participants. They do not automatically describe all people with ataxia telangiectasia. The registry does not report how entry into the extension or continued participation affected who contributed safety observations, which limits assessment of how representative the group may be.

Statistically, it is useful to distinguish the number of participants affected from the total number of adverse events. The record reports participant counts in the safety summary while describing the primary endpoint as a number of events. Keeping these quantities separate prevents the mistaken assumption that every affected participant experienced only one event. The follow-up timeframe and the absence of reported exposure-adjusted analyses are also relevant when interpreting simple counts.

Finally, the stated objectives and the available results are not the same thing. The registry names quality-of-life and neurological measures as additional outcomes, but numerical results for them are not reported in the registry record. This distinction matters when deciding what can be concluded: the safety observations can be described, while planned symptom or quality-of-life evaluations cannot be interpreted without their results and analysis details.

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 principal design limitation is the absence of a concurrent comparator. With a single group and no masking, the study cannot estimate a controlled difference in adverse events or other outcomes, and awareness of treatment may influence reporting or assessment in general. The extension population had participated in an earlier study, so the observations apply to this particular group; the registry record does not report information about people who did not enter or continue in the extension.

The safety summary provides counts of participants affected, a list of selected serious event terms, and reported percentages, but it does not give a complete event-level account. The total number of events, participant-level recurrence, event timing and duration, outcomes, and detailed relatedness assessments are not reported in the registry record. The primary outcome is described as a number of events, while the summary presents affected-participant counts, which are not interchangeable.

Follow-up could continue beyond the planned 12 months, with follow-up after the final visit or infusion. However, individual observation time and exposure-adjusted safety results are not reported in the registry record. This makes it difficult to interpret crude counts in relation to differences in how long participants were observed or treated.

Numerical results for the EQ-5D-5L, mICARS, and Clinical Global Impression outcomes are not reported in the registry record. The analysis plan, missing-data procedures, multiplicity approach, sample-size justification, interim analyses, and reason for termination are also not reported. These gaps prevent fuller assessment of outcome precision, completeness, and the analysis choices underlying the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study — NCT03563053.
• Registry record last updated 2024-10-08; status last verified 2024-09.
• Results first posted 2024-10-08.
• 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

NCT03563053 is a Phase 3, open-label, single-group extension study of the EryDex System in people with ataxia telangiectasia who participated in the ATTeST-IEDAT-02-2015 study. The registry lists 104 participants, a start date of 2018-06-12, a primary completion date of 2022-09-02, and a status of terminated. The reason for termination is not reported in the registry record.

The primary objective was long-term safety and tolerability. The posted safety summary records 12 participants affected by serious adverse events, 98 affected by other adverse events, and 0 deaths. Secondary and exploratory objectives concerned quality of life and neurological symptoms, but numerical results for those outcomes are not reported in the registry record. No concurrent comparator, randomized allocation, or masking is listed. The statistical analysis plan and key analysis details are not reported in the registry record.