This page separates reported trial information from statistical interpretation. The numerical trial information on this page is restricted to the ClinicalTrials.gov record data. ClinicalTrials.gov provides the official trial registry record. View NCT02134028 on ClinicalTrials.gov.
1. Trial at a Glance
LIBERTY ASTHMA TRAVERSE was a phase 3, single-group, unmasked treatment study evaluating the long-term safety of dupilumab in patients with asthma. The registry reports enrollment of 2282 participants and one primary binary endpoint: the number of participants with treatment-emergent adverse events.
| Feature | LIBERTY ASTHMA TRAVERSE |
|---|---|
| Trial name | LIBERTY ASTHMA TRAVERSE |
| Brief title | Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (LIBERTY ASTHMA TRAVERSE) |
| Phase | Phase 3 |
| Status | COMPLETED |
| Condition | Asthma |
| Therapeutic area | Pulmonology |
| Allocation | NA |
| Design model | SINGLE_GROUP |
| Masking | NONE |
| Primary purpose | TREATMENT |
| Enrollment | 2282 |
| Arms | 1 |
| Intervention | Dupilumab (drug) |
| Lead sponsor | Sanofi |
| Sponsor type | INDUSTRY |
| Start | 2014-08-05 |
| Primary completion | 2019-10-11 |
| Results posted | Yes |
| Primary endpoint type | Binary |
Registry interpretation: The trial is not described as a randomized comparison in the ClinicalTrials.gov record. Its design model is SINGLE_GROUP, with one arm and no masking. That design distinction is central to how the safety data should be interpreted.
2. Clinical Question
The registry describes LIBERTY ASTHMA TRAVERSE as a long-term safety evaluation of dupilumab in patients with asthma. The primary statistical question is therefore centered on the occurrence of treatment-emergent adverse events during the specified treatment-emergent period, rather than on a randomized comparison between two concurrent treatment groups.
Population
Patients with asthma enrolled in the LIBERTY ASTHMA TRAVERSE study.
Intervention
Dupilumab (drug).
Comparator
The ClinicalTrials.gov record does not identify a concurrent randomized comparator arm. The design is single-group.
Primary question
How many participants experienced treatment-emergent adverse events during the registered treatment-emergent AE period?
3. Trial Design
Dupilumab
- Intervention: Dupilumab (drug)
- Single-group study model
- Masking: none
- Primary purpose: treatment
LIBERTY ASTHMA TRAVERSE
- Enrollment: 2282
- Phase 3
- Condition: asthma
- Status: completed
The single-group structure changes the statistical interpretation substantially. A randomized two-arm efficacy trial can estimate a between-group treatment effect because randomization creates concurrent treatment groups. A single-group safety study instead primarily describes the frequency and characteristics of adverse events observed during exposure and follow-up. It does not, by itself, estimate a randomized causal difference between dupilumab and a concurrent control treatment.
4. Primary Endpoint
| Endpoint | Registry definition / time frame | Type |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks (up to 108 weeks) | Binary |
The registry defines an adverse event as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with treatment. Treatment-emergent adverse events are defined as adverse events that developed, worsened, or became serious during the treatment-emergent AE period.
5. Results Status and Planned Analysis
Results are posted in the ClinicalTrials.gov record, including safety counts by prior study and treatment exposure. However, the ClinicalTrials.gov record contains no formal statistical analyses: no formal statistical analyses were posted.
What would normally be analysed?
For a binary safety endpoint in a single-group study, the primary descriptive quantity would ordinarily be the number and proportion of participants experiencing at least one event during the prespecified treatment-emergent period. If a confidence interval were required, a binomial confidence interval could be used for the event proportion.
where x is the number of participants with the event and n is the number of participants in the analysis population. The ClinicalTrials.gov record does not provide a formal statistical-analysis result for the primary TEAE endpoint.
A formal p-value would generally require a prespecified null hypothesis or comparator. The ClinicalTrials.gov record does not provide such a hypothesis test for the primary endpoint.
6. Posted Safety Results by Prior Study and Treatment Exposure
The ClinicalTrials.gov record reports serious adverse events by prior study and treatment exposure. These counts are presented as affected participants divided by participants at risk.
| Prior study / exposure group | Serious adverse events | At risk |
|---|---|---|
| Participants From DRI12544 Study Placebo | 14 | 111 |
| Participants From DRI12544 Study Dupilum | 42 | 421 |
| Participants From EFC13579 Study Placebo | 48 | 517 |
| Participants From EFC13579 Study Dupilum | 106 | 1013 |
| Participants From EFC13691 Study Placebo | 12 | 97 |
| Participants From EFC13691 Study Dupilum | 10 | 90 |
7. How to Read the Safety Counts
A safety count such as 106/1013 means that 106 affected participants are reported among 1013 participants at risk in that specified group. The numerator is an event count and the denominator establishes the population from which the count was obtained.
Numerator
The number of participants identified as having the reported serious adverse event outcome in the specified group.
Denominator
The number of participants at risk for that reported group.
Participant-level interpretation
A participant count generally indicates whether participants experienced the event, rather than how many individual event episodes occurred.
Exposure context
Because the groups derive from prior studies and treatment exposure, direct comparisons require careful attention to how participants entered the long-term study.
8. Statistical Methodology
Binary endpoint analysis
The registered primary endpoint is binary: a participant either meets the registry definition of having a treatment-emergent adverse event during the specified period or does not. The natural descriptive summary is therefore a count and proportion.
For a participant-level binary outcome, the event proportion summarizes how common the outcome was in the defined analysis population. A confidence interval can quantify sampling uncertainty around that proportion when an inferential interval is prespecified.
Why a single-group design changes the analysis
In a randomized parallel-group trial, a treatment effect can be expressed as a risk ratio, risk difference, odds ratio, hazard ratio, or another between-group contrast. LIBERTY ASTHMA TRAVERSE is registered as a single-group study. Consequently, the primary endpoint is naturally interpreted as a safety-frequency measure rather than as a randomized treatment effect.
Descriptive safety analysis
Safety analyses commonly distinguish participants with at least one event from the total number of participants at risk. This avoids treating multiple events in the same participant as though they represented multiple independent participants. The ClinicalTrials.gov record does not provide the complete event-level dataset, so no event-rate calculation beyond the reported affected/at-risk counts is presented here.
Confidence intervals for a proportion
If a formal confidence interval for the primary binary endpoint were prespecified, a binomial confidence interval would be appropriate for the underlying event probability. The precise interval method should come from the statistical analysis plan rather than being inferred after observing the data.
Here, p represents the underlying probability that a participant experiences the specified binary outcome during the defined assessment period.
No formal comparative model reported
No formal statistical analyses were posted. Accordingly, there is no registry-reported odds ratio, risk ratio, risk difference, hazard ratio, confidence interval, or p-value to report for the primary endpoint.
9. Statistical Methods Explained
Why is the primary endpoint binary?
The registry endpoint asks for the number of participants with treatment-emergent adverse events. At the participant level, this creates a binary classification: the participant either meets the endpoint definition during the specified treatment-emergent period or does not.
Why is a single-group study different from a randomized trial?
A single-group study has no concurrent randomized treatment assignment against which the intervention can be contrasted. It can characterize observed safety outcomes, but an observed event proportion does not by itself establish how that proportion would have differed under another treatment.
What does 42/421 represent?
Within the reported DRI12544 Study Dupilum group, 42 participants are identified as having serious adverse events among 421 participants at risk. The fraction describes the observed participant-level event frequency in that reported group. It is not, by itself, a causal treatment effect estimate.
Why should prior-study groups not automatically be pooled?
The ClinicalTrials.gov record identifies three different prior studies and separate placebo and dupilumab exposure groups. Pooling them would require a prespecified rationale and an understanding of whether their populations, exposure histories, follow-up, definitions, and observation opportunities are sufficiently comparable. The registry summary reported here does not provide enough information to justify such a pooled analysis.
Why does the observation window matter?
The primary endpoint has a defined treatment-emergent period: from the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks, up to 108 weeks. Event frequencies depend on how long participants are observed and when events are considered treatment-emergent.
Why is a p-value not reported here?
A p-value requires a specified statistical hypothesis. The ClinicalTrials.gov record contains no formal statistical analysis for the primary endpoint and do not provide a null hypothesis against which the single-group safety proportion was tested.
10. What a Formal Safety Analysis Would Need to Specify
A complete statistical analysis plan for this type of safety study would normally define the analysis population, treatment-emergent period, handling of multiple events, coding conventions, denominators, missing data rules, and any confidence-interval methodology before reviewing the observed results.
| Statistical issue | Why it matters |
|---|---|
| Analysis population | The denominator determines which participants are considered at risk for the endpoint. |
| Treatment-emergent definition | Events outside the prespecified period may not contribute to the primary TEAE endpoint. |
| Participant vs event counting | A participant with multiple events should not automatically be counted as multiple affected participants for a participant-level binary endpoint. |
| Follow-up duration | Different observation opportunities can affect the number of observed adverse events. |
| Missing information | The analysis plan should specify how incomplete safety information is handled. |
| Confidence intervals | The method should be prespecified rather than selected solely after observing the event proportion. |
| Comparative inference | A treatment comparison requires a defined comparator or external reference and an appropriate statistical framework. |
11. Serious Adverse Events: Statistical Perspective
The serious-adverse-event data are particularly useful for demonstrating why denominators and study provenance matter. The registry separates participants according to both prior study and treatment exposure, producing six reported affected/at-risk combinations.
| Group | Affected / at risk | What can be stated directly |
|---|---|---|
| DRI12544 Study Placebo | 14 / 111 | 14 affected participants among 111 at risk |
| DRI12544 Study Dupilum | 42 / 421 | 42 affected participants among 421 at risk |
| EFC13579 Study Placebo | 48 / 517 | 48 affected participants among 517 at risk |
| EFC13579 Study Dupilum | 106 / 1013 | 106 affected participants among 1013 at risk |
| EFC13691 Study Placebo | 12 / 97 | 12 affected participants among 97 at risk |
| EFC13691 Study Dupilum | 10 / 90 | 10 affected participants among 90 at risk |
These data support descriptive statements about the number of affected participants in each reported group. They do not, without additional design and analysis information, establish that differences between the groups are attributable to dupilumab. Participants came from different prior studies, and the current trial itself is registered as single-group.
12. Interpreting Safety Without Overstating Causality
An adverse event is not necessarily caused by treatment. The registry definition explicitly states that an adverse event does not necessarily have a causal relationship with treatment. Therefore, the number of TEAEs should be interpreted as an observed safety outcome under the registry definition, not automatically as the number of adverse effects caused by dupilumab.
A participant-level count describes how many participants experienced an outcome. It does not necessarily describe how many total event episodes occurred, how long events lasted, or how severe each event was.
Even when placebo and dupilumab exposure groups appear in the posted serious-adverse-event data, those groups are not equivalent to a randomized placebo-controlled comparison within LIBERTY ASTHMA TRAVERSE. The current study is registered as single-group.
A numerical event proportion describes the observed frequency. A confidence interval, if provided, would describe statistical uncertainty around that estimated proportion. The ClinicalTrials.gov record does not provide formal confidence intervals for the posted safety counts.
13. Longitudinal Trial History
Study start
The registry lists 2014-08-05 as the start date for LIBERTY ASTHMA TRAVERSE.
Primary completion
The registry lists 2019-10-11 as the primary completion date.
Registry status
The ClinicalTrials.gov record identifies the study status as COMPLETED and reports results as posted.
The ClinicalTrials.gov record does not provide a detailed publication-by-publication statistical timeline, interim analysis plan, or separate analysis cutoffs. Those details are therefore not inferred here.
14. Design Topics Not Supported by the ClinicalTrials.gov record
Several statistical topics that are important in randomized clinical trials are not supported by the registry-reported LIBERTY ASTHMA TRAVERSE data. They should not be retrofitted into the analysis simply because they appear on other trial-results pages.
| Topic | Status in the ClinicalTrials.gov record |
|---|---|
| Non-inferiority margin | Not reported. |
| Crossover | Not reported. |
| Factorial design | Not reported; the design model is SINGLE_GROUP. |
| Formal multiplicity strategy | Not reported. |
| Interim analysis | Not reported. |
| Missing-data / imputation strategy | Not reported. |
| Randomization stratification | Not reported; allocation is listed as NA. |
| Bayesian methods | Not reported. |
| Formal statistical analyses | None in the posted results. |
15. Safety Analysis Framework
For a long-term safety study, several layers of analysis can coexist. The primary endpoint is a participant-level binary TEAE outcome, while additional safety summaries can characterize serious adverse events and other safety categories. These layers answer different questions.
Any TEAE
Whether a participant experienced at least one treatment-emergent adverse event during the registered treatment-emergent period.
Serious adverse events
The ClinicalTrials.gov record provides affected participants and participants at risk for six prior-study/exposure groups.
Severity
The ClinicalTrials.gov record does not provide a complete severity distribution for the primary endpoint.
Causality
An adverse event does not necessarily have a causal relationship with treatment under the registry definition.
16. Limitations
- No formal statistical analyses reported: No formal statistical analyses were posted, so no registry-reported effect estimates, confidence intervals, or p-values are available for the primary endpoint.
- Single-group design: The current study is registered as SINGLE_GROUP, limiting direct causal comparison with a concurrent control group.
- Safety endpoint interpretation: The primary endpoint records treatment-emergent adverse events, but an adverse event does not necessarily have a causal relationship with treatment.
- Prior-study provenance: The reported serious-adverse-event groups come from three prior studies and are separated by prior treatment exposure.
- Different denominators: The six serious-adverse-event groups have different numbers of participants at risk, so raw event counts alone are not directly comparable.
- Observation time: The primary TEAE endpoint uses a defined treatment-emergent period, which must be considered when interpreting event frequency.
- Incomplete methodological detail: The ClinicalTrials.gov record does not report formal missing-data handling, multiplicity procedures, interim monitoring, stratification, or Bayesian methodology.
- No unsupported reconstruction: It would be inappropriate to create unreported comparative statistics or confidence intervals from the registry-reported summary counts alone.
17. Why This Trial Matters Statistically
LIBERTY ASTHMA TRAVERSE is a useful teaching example because it demonstrates an important distinction in clinical-trial statistics: a large phase 3 study does not necessarily imply a randomized treatment-effect analysis. The design, endpoint definition, denominator, and source population determine what statistical conclusions are justified.
| Concept | How it appears in LIBERTY ASTHMA TRAVERSE |
|---|---|
| Single-group design | The registry identifies the design model as SINGLE_GROUP. |
| Binary endpoint | The registered primary endpoint is the number of participants with TEAEs. |
| Safety analysis | The study is a long-term safety evaluation of dupilumab in asthma. |
| Participant-level counting | The primary endpoint is defined in terms of participants with TEAEs. |
| Defined observation window | The primary endpoint extends from the first IMP injection through the last IMP injection plus 14 weeks, up to 108 weeks. |
| Denominator interpretation | Posted serious-adverse-event results specify affected participants and participants at risk. |
| External comparison caution | Prior-study placebo and dupilumab groups are not equivalent to a randomized comparator in the current single-group study. |
| Missing formal inference | No statistical analyses are reported in the ClinicalTrials.gov record. |
| Causal interpretation | An adverse event does not necessarily have a causal relationship with treatment. |
| Registry-based analysis | The analysis distinguishes directly reported information from general statistical methodology. |
18. Statistical Concepts in This Trial
Learn more about the methods used in this trial:
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: NCT02134028 — LIBERTY ASTHMA TRAVERSE.
- Linked PubMed record: PMID 42548408.
- Linked PubMed record: PMID 40767333.
- Linked PubMed record: PMID 40458676.
- Linked PubMed record: PMID 39424189.
- Linked PubMed record: PMID 39155737.
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21. Record Summary
LIBERTY ASTHMA TRAVERSE is a completed phase 3, single-group study of dupilumab in patients with asthma, with enrollment of 2282.0 participants and one registered primary binary endpoint concerning treatment-emergent adverse events. The primary endpoint is defined over a specific treatment-emergent AE period extending from the first IMP injection in LTS12551 to the last IMP injection plus 14 weeks, up to 108 weeks.
The key statistical point is that the registry's SINGLE_GROUP design and the absence of registry-reported formal statistical analyses constrain the conclusions that can be drawn. The posted serious-adverse-event counts provide affected participants and denominators for six prior-study and exposure groups, but those groups should not be treated as a concurrent randomized comparison within LIBERTY ASTHMA TRAVERSE.