Continuation of TRAVERSE- LTS12551 Evaluating Dupilumab Safety in Patients With Asthma (Long-Term Follow-Up): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Continuation of TRAVERSE- LTS12551 Evaluating Dupilumab Safety in Patients With Asthma (Long-Term Follow-Up) (NCT03620747), a na phase 3 study. The primary outcome is Percentage of Participants With Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

This is a descriptive safety question, not a test of whether dupilumab is more effective or safer than an alternative. The registry record defines a treatment-emergent adverse event as an event that developed, worsened, or became serious during the specified period. It also notes that an adverse event did not necessarily have to be causally related to treatment.

The posted registry information gives some adverse-event counts and lists several serious adverse-event terms. It does not report the result for the primary endpoint: the percentage of participants with treatment-emergent adverse events, or its 95% confidence interval, is not reported in the registry record. The numerical safety summaries therefore offer only a partial account of the primary question.

3. Trial Design

This was an open-label, interventional, single-group cohort study in Phase 3. It enrolled 393 participants with asthma who had completed the TRAVERSE-LTS12551 trial. The registry record describes the target population as people with moderate to severe asthma. The study was sponsored by Sanofi and is listed as completed.

Participants received dupilumab, identified in the intervention record as Dupilumab SAR231893 (REGN668). The stated regimen was a subcutaneous dose of 300 mg every 2 weeks from Week 0 up to Week 132. Participants who discontinued treatment for at least 6 weeks after study LTS12551 received a 600 mg loading dose at Week 0. The registry record describes follow-up for the primary endpoint from the first dose of investigational medicinal product up to 12 weeks after the last dose, with a maximum duration of up to 144 weeks.

The study began on 2018-08-30, and primary completion is listed as 2022-02-18. No random allocation or masking was used; the registry lists allocation as not applicable and masking as none. Because all participants were in a single treatment group, the design can describe events observed during follow-up but cannot directly compare those observations with a concurrent control group.

The study's stated aim was long-term safety follow-up after completion of the earlier asthma trial. It is therefore important to distinguish this cohort from a randomized treatment comparison. Enrollment describes the study, while the endpoint population was defined by actual receipt of at least one dose or part of a dose of study drug. The registry record does not report further details about the study's sample-size justification or the rationale for its design.

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.

Before assignment: Participants with moderate to severe asthma who had completed the parent study TRAVERSE-LTS12551 (NCT02134028) were enrolled in this current study (LPS15023).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on safety population that included all participants who had actually received at least one dose or part of a dose of IMP.

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: Analysis was performed on all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), measured over From first dose of IMP up to 12 weeks after last dose of IMP (maximum duration: up to 144 Weeks).

The primary endpoint was the percentage of participants with treatment-emergent adverse events (TEAEs). The registry defines an adverse event as an untoward medical occurrence in someone who received study drug; a causal relationship to treatment was not required. An event was treatment-emergent if it developed, worsened, or became serious during the TEAE period.

The observation period began with the first dose of investigational medicinal product and continued up to 12 weeks after the last dose. The registry gives a maximum duration of up to 144 weeks. The endpoint therefore describes whether participants experienced at least one event meeting the treatment-emergent definition during that period, rather than estimating the number of events per unit of follow-up time.

As a general statistical explanation, a participant-level percentage is useful for describing how commonly an event affected people in a defined population and observation window. It does not, by itself, show how many total events occurred, how long participants were observed, or whether an event was caused by treatment. These distinctions matter because one participant may experience multiple events, and events can have different severity and clinical meaning.

The registry record identifies the endpoint and its confidence-interval type as 95% confidence interval, but it does not report the primary endpoint's percentage or interval estimate. Those numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a percentage of participants and specifies a 95% confidence interval as the measure of dispersion. It defines the safety population as participants who actually received at least one dose or part of a dose of investigational medicinal product. These definitions determine who contributes to the safety summary and what counts as an event during the analysis period. However, the registry record does not report the primary endpoint estimate or the method used to calculate its interval.

What does a participant percentage describe?

As a general explanation, a participant percentage describes the share of a defined analysis population that met an event criterion within a defined observation window. For an endpoint based on whether participants experienced treatment-emergent events, the unit being summarized is the participant, not each separate occurrence. A participant with several events may still contribute as a participant who experienced an event for this type of summary. Event counts and participant counts answer different questions, so they should not be treated as interchangeable.

The endpoint's time window is part of its definition. In this study, it runs from the first dose of investigational medicinal product to 12 weeks after the last dose, with a maximum duration of up to 144 weeks. An event outside that window would not meet the stated time criterion for this endpoint. The record's definition also includes events that developed, worsened, or became serious in the period, and does not require a causal link to study drug.

How should a confidence interval be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the statistical method and its assumptions. A narrower interval indicates greater precision than a wider interval, while neither width nor location alone determines whether an event was caused by treatment. A 95% confidence interval is a conventional way to express uncertainty in an estimate. The registry specifies this interval level for the primary outcome, but the actual interval is not reported in the registry record.

Intervals for participant percentages often rely on a method suited to proportions. The exact method matters, especially when event counts are small or estimates are near the boundaries of the possible range. The registry record does not report the confidence-interval method, so the interval's construction cannot be evaluated. No method should be inferred from the endpoint label alone.

Why does the single-group design matter?

As a general principle, a single-group study can describe events observed in its enrolled cohort, but it lacks a concurrent group to separate treatment exposure from other influences. Randomization can help make groups comparable on average, while masking can reduce some forms of bias in ascertainment. Neither feature is listed for this study: allocation is recorded as not applicable and masking as none. This means the safety findings are descriptive and should not be read as a randomized estimate of excess risk or comparative safety.

Open-label status can also matter for how events are noticed, reported, assessed, and recorded. This is a general methodological consideration, not evidence that the study's assessments were biased. The registry record does not describe any specific procedures used to reduce or assess such possible influences.

What is and is not reported about the analysis?

The registry lists four outcome measures and no analyses. It does not report a detailed statistical analysis plan, adjustment methods, a missing-data method, or a method for handling repeated events. The primary endpoint's percentage and confidence interval are also not reported. Consequently, the posted record supports an explanation of the intended endpoint and its population, but not a full audit of the numerical analysis.

As a general explanation, repeated events within a participant can create dependence: one person's event history may not provide the same information as an equal number of events spread across different people. For event counts, over-dispersion can arise when variability exceeds what a simple count model assumes. Methods that account for within-participant clustering or excess variability may then be relevant. This is a general statistical issue; the registry record does not report whether repeated-event models or over-dispersion adjustments were used in this study.

The record also includes planning assumptions for an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence of the study's own design or observed power. No planning estimates are reported in the registry record, and the single-group trial design should not be mistaken for the equal-allocation comparison described by those illustration assumptions. The trial's own sample-size justification is not reported in the registry record.

In general, planning estimates depend on the effect size, variability, analysis method, and design assumptions. They are not a substitute for observed results, and a planned power target does not establish the probability that a particular finding is true. Because the relevant calculated planning values and the trial's own design rationale are not reported in the registry record, no numerical planning conclusion can be drawn from the registry summary.

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("Dupilumab")
n      <- c(393)
events <- c(214)
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  Dupilumab  393  214  54.5  49.4  59.5  49.5  59.3  49.5  59.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and secondary outcomes concerning adverse events of special interest, treatment-emergent serious adverse events, and adverse events leading to study discontinuation. It reports four outcome measures but no analyses. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment for evaluating several outcomes. Without that information, the control of false-positive findings across multiple statistical tests cannot be assessed. This is especially relevant when many outcomes or event categories are examined; as a general principle, considering more tests can increase the chance of at least one apparently unusual result.

The registry record does not report how missing outcome data were handled, whether all participants completed follow-up, or whether follow-up time differed across participants. The endpoint's observation window is defined, and the safety population includes participants who received at least part of a dose, but those definitions do not explain how incomplete observations were treated. No assumptions about the reasons for missing data or their statistical handling should be inferred.

The registry does not report whether participants who stopped treatment remained under observation, or how events after discontinuation were assessed beyond the stated endpoint window. Nor does it report sensitivity analyses for missing data. These details can affect interpretation of a safety proportion, because the opportunity to observe events depends on the time and completeness of follow-up.

The stated analysis population is the safety population: participants who actually received at least one dose or part of a dose of investigational medicinal product. The registry record does not report additional analysis populations or explain how deviations from treatment were handled. As a general point, population definitions can differ across analyses, so an endpoint result is interpretable only with its analysis population and missing-data approach clearly specified. The primary endpoint result itself is not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (1.0%), covid-19 (0.8%), covid-19 pneumonia (0.8%), cardiac failure congestive (0.3%), myocardial infarction (0.3%).

The registry's adverse-event summary lists 22 participants affected by serious adverse events and 93 affected by other adverse events, with 393 at risk for each category. It lists 5 deaths. These are distinct summary entries, and the registry record does not say that the categories are mutually exclusive. They should not be added together to create a participant total.

For serious adverse-event terms, the record lists Asthma at 1.0%, COVID-19 at 0.8%, COVID-19 pneumonia at 0.8%, Cardiac failure congestive at 0.3%, Myocardial infarction at 0.3%, and Epilepsy at 0.3%. These term-specific percentages are part of the posted summary. They are not estimates of treatment-attributable risk, and the registry record does not report a causal assessment for these events.

The endpoint definition states that an adverse event did not have to be causally related to study drug. A death entry also does not, by itself, establish that study treatment caused the death. The registry record does not report causes of death or a treatment-relatedness assessment for the listed deaths. The counts should therefore be read as safety observations recorded in the cohort, not as proof of a treatment effect.

As a general statistical point, adverse-event summaries depend on definitions, follow-up duration, and how events are classified. The primary TEAE percentage and confidence interval are not reported in the registry record, so the listed serious-event information cannot be used to reconstruct that primary result.

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

The study addresses long-term safety description among participants with moderate to severe asthma who completed TRAVERSE-LTS12551 and then received dupilumab in an open-label, single-group cohort. The registry reports selected adverse-event counts and serious-event term percentages. These data describe what was recorded among participants in the study; they are not a randomized comparison against another treatment or a no-treatment group.

The primary endpoint was the percentage of participants with treatment-emergent adverse events during the specified period, but that percentage and its 95% confidence interval are not reported in the registry record. Without the estimate, the primary outcome's observed frequency and precision cannot be assessed from the posted record. The other safety summaries do not fill that gap because they refer to serious events, other events, deaths, or selected event terms rather than providing the missing primary endpoint result.

The findings also do not establish that any reported event was caused by dupilumab. The event definition expressly does not require a causal relationship. The single-group design lacks a concurrent comparator, and the registry does not provide a basis for estimating what would have happened to a comparable group under a different exposure. As a general principle, observed events in an uncontrolled cohort can reflect multiple influences, including underlying illness and events occurring during follow-up.

The posted information does not report a treatment-effect estimate, a comparative risk, or a complete account of missing data and analysis methods. It therefore cannot support a conclusion about comparative safety or efficacy. The study's stated purpose is safety follow-up, not a randomized efficacy evaluation.

The most defensible reading is limited to the study's stated design and reported observations: this was a completed safety cohort, with listed adverse-event summaries and a defined primary endpoint. The main endpoint result, its uncertainty, and the details needed for broader causal or comparative conclusions are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical biostatistics: a safety objective can be descriptive even when the endpoint is expressed as a percentage and accompanied by a confidence interval. The percentage would quantify the observed share of participants meeting the event definition, while the interval would convey uncertainty under its statistical assumptions. Neither quantity, by itself, establishes causation or provides a comparison with another treatment.

The single-group design is central to interpretation. Long-term follow-up can document events in a population that has completed an earlier trial, but the absence of a concurrent comparator limits what can be attributed specifically to study treatment. The open-label design also makes it useful to ask how events were assessed and recorded. Those methodological details are not reported in the registry record.

The endpoint definition shows why careful outcome language matters. Treatment-emergent describes timing and event status within a specified period; it does not mean treatment-caused. Similarly, counts for serious events, other events, and deaths are different kinds of summaries and should not be combined or treated as interchangeable. The serious-event term percentages give additional descriptive detail, but do not replace the unreported primary endpoint estimate.

Finally, the record demonstrates that registration details and numerical analysis results are not always equally complete. The population and endpoint definitions are described, but the primary percentage, its confidence interval, and key analysis details are not reported in the registry record. Recognizing what is reported and what remains unavailable is part of sound statistical interpretation, particularly when safety observations might otherwise be mistaken for comparative 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.

The primary limitation for interpreting the posted safety results is that the registry record does not report the primary TEAE percentage or its 95% confidence interval. The endpoint is defined, but its numerical result and precision are unavailable in the record. The posted serious-event counts and term percentages cannot substitute for that result.

The study was open-label and single-group, with no concurrent comparator. Consequently, its adverse-event summaries cannot estimate a randomized difference between dupilumab and another treatment, nor can they separate treatment effects from other influences on event occurrence. This limitation is specific to the design described in the registry record; it does not determine the direction or size of any possible bias.

The cohort consisted of participants who had completed TRAVERSE-LTS12551, and the safety population was defined by receipt of at least one dose or part of a dose. The registry does not report enough information to assess how this selection may relate to people with asthma outside that study population. Generalizing beyond the described cohort therefore requires caution.

The registry record does not report the statistical analysis plan, the confidence-interval method, missing-data handling, follow-up completeness, multiplicity procedures, or sensitivity analyses. It also does not report causes of death or treatment-relatedness assessments for the listed adverse events. These omissions limit evaluation of precision, potential bias, and causal interpretation. They should be treated as unreported information, not as evidence that a particular method or procedure was or was not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Continuation of TRAVERSE- LTS12551 Evaluating Dupilumab Safety in Patients With Asthma (Long-Term Follow-Up) — NCT03620747.
• Registry record last updated 2023-03-16; status last verified 2023-02.
• Results first posted 2023-03-16.
• 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

NCT03620747 is a completed Phase 3, open-label, interventional, single-group cohort study sponsored by Sanofi. It enrolled 393 participants with asthma who had completed TRAVERSE-LTS12551; the stated population had moderate to severe asthma. Participants received subcutaneous dupilumab every 2 weeks from Week 0 up to Week 132, with a 600 mg Week 0 loading dose for participants who had discontinued treatment for at least 6 weeks after the earlier study.

The primary objective was to describe long-term safety. The primary endpoint was the percentage of participants with treatment-emergent adverse events from first dose up to 12 weeks after the last dose, with a maximum duration of up to 144 weeks. The registry lists serious-event and other-event counts, deaths, and selected serious-event terms, but the primary TEAE percentage and 95% confidence interval are not reported in the registry record. The record also does not report a concurrent comparator, detailed analysis methods, or missing-data procedures.