This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (NCT04537377), a na phase 1, phase 2 study. The primary outcome is Safety and Tolerability Profile (Including Treatment-emergent Adverse Events (TEAE)) - Number of Participants.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04537377 |
| Phase | Phase 1, Phase 2 |
| Condition | Wilson's Disease |
| Allocation | Not applicable (single group) |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vivet Therapeutics SAS |
| Results posted | Yes |
2. Clinical Question
Population
Adults with Wilson's Disease enrolled in the study. The registry record lists enrollment of 4 participants and identifies the safety analysis population as the Safety Analysis Set.
Intervention
A single intravenous dose of VTX-801, a gene therapy, in ascending dose cohorts. The study description says safety, tolerability, and pharmacological activity are assessed before and following withdrawal of background Wilson's Disease therapy.
Comparator
There is no randomized control group. The record describes a non-randomized, sequential study, and the dose cohorts are not like-for-like control groups. Any differences between their observed counts are descriptive.
Primary question
What safety and tolerability profile, including treatment-emergent adverse events, is observed after VTX-801? The primary outcome is the number of participants with safety events through the primary completion visit, an average of 1 year.
The clinical question is exploratory rather than a conventional comparison of an assigned intervention against a control. The study is Phase I/II, open label, and uses a single-dose escalation design. The registry lists VTX-801 dose cohorts of 5E12 VG/kg and 1.5E13 VG/kg. With only 4 participants enrolled overall, each cohort's safety counts describe a very limited set of observations. They cannot establish how event patterns would compare in larger or different populations.
The record also names pharmacological measures, including free serum copper, total serum copper, 24-hour urinary copper, and serum ceruloplasmin activity, as well as VTX-801 responder status. The main purpose described is to assess safety, tolerability, and pharmacological activity over follow-up of up to 5 years. Numerical results for those measures are not reported in the registry record. The main question that can be addressed from the posted results is therefore descriptive: which safety events and deaths are recorded in each dose cohort, and what limits apply to interpreting those counts?
3. Trial Design
This is a Phase I/II, multicenter, non-randomized, open-label study with an adaptive design and sequential dose escalation. It is described as a single-dose study with 5-year follow-up. The intervention is VTX-801, administered intravenously to adults with Wilson's Disease. The study's stated objectives are to assess safety, tolerability, and pharmacological activity for up to 5 years, before and following withdrawal of background Wilson's Disease therapy.
The registry lists enrollment of 4 participants, with dose cohorts of 5E12 VG/kg and 1.5E13 VG/kg. There is no randomized allocation and no masked treatment assignment. These features matter statistically: the cohort counts are not results from a randomized head-to-head comparison, and differences between cohorts could reflect factors other than dose. The record does not report the detailed sequence or rules used to assign participants to dose cohorts, nor does it report the adaptive design rules.
The study started on 2021-09-03, has primary completion listed as 2024-12-17, and is marked active, not recruiting. These registry fields describe study status and timing; they do not, by themselves, establish that every planned follow-up period has finished or that all outcomes have been analyzed. The primary safety timeframe is through the primary completion visit, an average of 1 year, while the broader study description specifies follow-up for up to 5 years.
The primary outcome concerns the number of participants with safety events, including treatment-emergent adverse events. Named secondary measures concern copper and ceruloplasmin measures and responder status. The registry record does not report a sample-size justification, detailed dose-escalation protocol, or outcome analysis results beyond the listed adverse event counts. The design label alone is not enough to infer how the adaptive features operated in practice.
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: The study was prematurely terminated by the Sponsor for futility reasons, after insufficient pharmacodynamic response in cohorts 1 and 2. No further patient enrollment occurred after this date. The 4 treated patients entered the long-term follow-up (LTFU) up to 5 years post injection, thus 2 sites remain active. An abbreviated CSR was issued including all data until early termination (an average of 1 year). The LTFU results will be provided in a separate addendum at the end of 2029.
Overall Study
| Stage | VTX-801 5E12 VG/kg | VTX-801 1.5E13 VG/kg |
|---|---|---|
| STARTED | 2 | 2 |
| End of Primary Completion Period | 2 | 2 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 2 | 2 |
Reasons for not completing this period:
| Reason | VTX-801 5E12 VG/kg | VTX-801 1.5E13 VG/kg |
|---|---|---|
| Long term follow-up | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: 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.
| Characteristic | Unit | VTX-801 5E12 VG/kg | VTX-801 1.5E13 VG/kg | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | |
| Age, Continuous | years | 36.5 (SD 17.68) | 32.0 (SD 18.38) | 34.3 (SD 14.95) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 2 | 2 | 4 |
| Smoking History: Yes | Participants | 0 | 0 | 0 |
| Smoking History: No | Participants | 2 | 2 | 4 |
| Alcohol Consumption: Yes current | Participants | 1 | 0 | 1 |
| Alcohol Consumption: Yes former | Participants | 1 | 0 | 1 |
| Alcohol Consumption: No | Participants | 0 | 2 | 2 |
| BMI | kg/m^2 | 25.4 (SD 2.0) | 29.7 (SD 4.64) | 27.6 (SD 3.83) |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability Profile (Including Treatment-emergent Adverse Events (TEAE)) - Number of Participants, measured over through primary completion visit, an average of 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled Safety and Tolerability Profile, including treatment-emergent adverse events, and is measured as the number of participants. Events are summarized according to their onset date, by system organ class and preferred term, by dose cohort and overall. The stated population is the Safety Analysis Set. The timeframe is through the primary completion visit, an average of 1 year.
Counting participants with events is useful in an early-phase safety study because it describes how many people experienced an event, rather than treating repeated events in one person as if they occurred in separate participants. That distinction is important: participant counts and event counts answer different questions. A participant may experience more than one event, and the registry record does not provide the event-level results needed to characterize recurrence or duration.
The endpoint is used to organize safety observations during the study and to describe their types and timing. It is not a direct measure of comparative efficacy. The posted results list serious adverse event and other adverse event participant counts by dose cohort, but a complete numerical result for the primary endpoint by event category is not reported in the registry record. Nor are estimates of uncertainty for the primary endpoint reported there. The counts therefore support a limited descriptive account, not a precise estimate of the underlying frequency of events in a broader population.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a study with 4 participants across two dose cohorts, without randomization or a control arm. Its safety counts should be read as observations among these enrolled participants. The counts do not estimate a controlled treatment contrast, and the cohorts cannot be treated as equivalent groups assigned to different interventions. The listed dose groups are relevant for organizing the observations, but the record does not establish that any difference between them is attributable to dose.
For the 5E12 VG/kg cohort, the record lists 2 participants at risk for serious adverse events and 0 affected; for the 1.5E13 VG/kg cohort, it lists 2 at risk and 1 affected. For other adverse events, the record lists 2 participants at risk and 2 affected in each cohort. Deaths are listed as 0 in each cohort. These are small counts, so each participant's experience has substantial influence on the displayed pattern. The counts should not be read as stable estimates of event frequency or as evidence of a difference between doses.
Drug-Induced Liver Injury is listed among the top serious terms at 50.0%. The registry record does not report the denominator or additional context for this percentage in the record summarized. It should therefore be interpreted only as a listed term and percentage, not as a complete account of causality, severity, duration, or clinical course. The record also does not provide event-level timing or identify whether one participant experienced multiple events.
The primary outcome is a participant count, but a full primary endpoint result organized by event category is not reported in the registry record. No analysis records are listed, and inferential estimates such as confidence intervals or p-values are not reported. This limits the precision with which the safety pattern can be described. A confidence interval, as a general statistical concept, represents uncertainty around an estimated quantity; without a reported interval or enough detail to reconstruct the intended analysis, the uncertainty cannot be summarized as an endpoint estimate.
The study's early-phase, non-randomized design is appropriate to describing initial experience, but does not support a causal comparison of dose cohorts. Open-label observation can also influence how events are recognized, reported, or assessed; the record does not report procedures that would quantify or remove that possibility. In short, the posted counts document adverse events among the participants enrolled, but do not establish a comparative safety profile or a population-level event rate.
9. Statistical Methods Explained
The primary outcome is a count of participants with events. In general, an event indicator records whether a participant experienced an event, while an event count records how many events occurred. Those are not interchangeable: repeat events in one participant can increase an event count without increasing the number of affected participants. The registry describes the primary outcome as the number of participants and states that treatment-emergent adverse events are summarized by onset date, event category, dose cohort, and overall.
What does a descriptive count tell us?
A descriptive count reports what happened in the observed study group. It does not, by itself, estimate how often an event would occur in a broader population with useful precision. In this study, the listed groups contain very few participants. The serious adverse event counts and other adverse event counts are therefore best understood as a record of individual observed experiences, rather than as stable estimates. A change of experience in a single participant would materially change the pattern of counts.
Counts also need a clear denominator. The registry supplies numbers at risk and affected for the adverse event groups, but the listed Drug-Induced Liver Injury term is accompanied by 50.0% without a denominator described in the registry record. A percentage is most interpretable when its population, time period, and event definition are clear. The missing denominator and context prevent a more detailed interpretation of that term's percentage.
Why are confidence intervals and tests relevant?
As a general statistical concept, a confidence interval conveys the uncertainty around an estimate. For a small study, uncertainty is especially important because the observed count may be strongly influenced by individual participants. An interval would not remove the limitations of a small, non-randomized study, but it would make the imprecision of an estimate more visible. The registry record does not report confidence intervals for the listed safety results.
Hypothesis tests and p-values address whether data are compatible with a specified statistical model and null hypothesis. They do not establish clinical importance or prove that one dose is safer than another. No analysis records or p-values are reported in the registry record. Given the lack of randomization and a control group, a formal test of cohort differences would not solve the design's confounding limitations in any case.
How should the planning illustration be read?
The sample-size planning assumptions describe an illustration computed from an observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. Time-to-event calculations use the total number of events; other calculations use participants per arm. These are planning conventions, not observed study outcomes. Sample sizes derived from such assumptions are illustrations of what a hypothetical future design might require; they are not observed power, and they do not demonstrate that the current study had adequate power.
The numerical planning outputs and the effect used for those calculations are not reported in the registry record. Because this study is sequential and non-randomized, the illustration's equal-allocation assumption should not be mistaken for the actual enrollment structure or a randomized comparison. The record does not report a sample-size justification for the trial itself.
What can be inferred from the design?
The registry labels the design adaptive and sequential, but does not report the operating rules that governed dose escalation or adaptation. In general, a design label does not reveal which data triggered a decision, what stopping rules were used, or how statistical error was controlled. Those details are not reported in the registry record, so they cannot be inferred from the label alone. Likewise, the record does not report a detailed statistical analysis plan for the primary outcome.
Over-dispersion is a general concern when a count outcome varies more than a statistical model expects. It can arise when participants differ substantially or when events cluster within participants. That concern is relevant to repeated adverse events, but the primary endpoint is framed as participants with events, and event-level data are not reported. There is not enough information in the registry record to assess over-dispersion or select a model for repeated event counts.
Finally, the registry identifies the Safety Analysis Set as the primary endpoint population. It does not provide a separate account of exclusions, missing observations, or the exact analysis rules applied to that set. As a result, the methods that could be independently checked are limited to the stated outcome definition, timeframe, population, and descriptive adverse event counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and names secondary outcomes covering free serum copper, total serum copper, 24-hour urinary copper, serum ceruloplasmin activity, and VTX-801 responder status. It also lists six outcome measures overall. The record does not report a multiplicity strategy describing how interpretation would account for examining several outcomes or event categories. Without such a strategy, a reader cannot determine whether any reported statistical tests would have been adjusted or which outcomes were intended to support confirmatory conclusions. No analyses are listed in the registry record.
Missing-data handling is not reported in the registry record. In general, missing observations can affect an outcome summary if the probability of missingness differs across participants or relates to their health or event experience. The record does not specify how missed visits, incomplete follow-up, or unavailable measurements were handled, so no assumptions about those cases should be made.
The primary outcome population is the Safety Analysis Set. The registry record does not report the detailed membership rules for that set or describe additional analysis populations. It is therefore unclear from the record how participants with incomplete dosing or follow-up, if any, would be treated analytically. The record also does not report a statistical analysis plan, interim analysis approach, or sample-size justification. These omissions restrict the ability to evaluate how the outcomes were selected, analyzed, and interpreted.
These are reporting limitations, not evidence that a particular method was or was not used. The available record identifies the named outcomes and the safety population, but does not report the operational details needed to assess multiplicity, missingness, or analysis-population decisions.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| VTX-801 5E12 VG/kg | 0 | 2 | 0.0% |
| VTX-801 1.5E13 VG/kg | 1 | 2 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| VTX-801 5E12 VG/kg | 0 of 2 |
| VTX-801 1.5E13 VG/kg | 0 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| VTX-801 5E12 VG/kg | 2 of 2 |
| VTX-801 1.5E13 VG/kg | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | VTX-801 5E12 VG/kg | VTX-801 1.5E13 VG/kg |
|---|---|---|---|
| Drug-Induced Liver Injury | Hepatobiliary disorders | 0 of 2 | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | VTX-801 5E12 VG/kg | VTX-801 1.5E13 VG/kg |
|---|---|---|---|
| Fatigue | General disorders | 2 of 2 | 2 of 2 |
| Alanine Aminotransferase Increased | Investigations | 2 of 2 | 2 of 2 |
| Constipation | Gastrointestinal disorders | 0 of 2 | 2 of 2 |
| Lymphocyte Count Decreased | Investigations | 1 of 2 | 1 of 2 |
| Infusion Related Reaction | Injury, poisoning and procedural complications | 1 of 2 | 1 of 2 |
| Headache | Nervous system disorders | 1 of 2 | 1 of 2 |
| Tremor | Nervous system disorders | 2 of 2 | 0 of 2 |
| Abdominal Pain Upper | Gastrointestinal disorders | 1 of 2 | 0 of 2 |
| Diarrhoea | Gastrointestinal disorders | 1 of 2 | 0 of 2 |
| Nausea | Gastrointestinal disorders | 0 of 2 | 1 of 2 |
Serious events with the highest arm-level rate: drug-induced liver injury (50.0%).
The serious adverse event counts are presented by dose cohort. In the 5E12 VG/kg cohort, 2 participants were listed at risk and 0 were affected; in the 1.5E13 VG/kg cohort, 2 were listed at risk and 1 was affected. Deaths are listed as 0 for each cohort. For other adverse events, 2 participants were listed at risk and 2 were affected in each cohort.
These figures count participants, not necessarily the total number of events. They do not show how many events each affected participant experienced, how long events lasted, or their course. The registry also lists Drug-Induced Liver Injury at 50.0% among the top serious terms, but the denominator and additional context for that percentage are not reported in the registry record. The term alone does not establish cause or severity for any individual participant.
The cohorts are small and non-randomized, so their counts are descriptive rather than a valid controlled comparison. Zero deaths in the listed groups means no deaths are recorded in those participants; it does not establish the absence of risk in a larger population or over a longer period. The counts should be interpreted as the observed safety record, with substantial uncertainty and limited generalizability.
12. What the Result Does, and Does Not, Mean
The posted results show that serious adverse events were recorded for 0 participants in the 5E12 VG/kg cohort and 1 participant in the 1.5E13 VG/kg cohort. Other adverse events were recorded for 2 participants in each cohort, and deaths were listed as 0 in both. These observations describe the enrolled participants; they do not establish what would occur in a larger population.
The counts do not demonstrate that one dose has a different safety profile from the other. Participants were not randomized, there was no control group, and each cohort included only 2 participants at risk. Differences in observed counts may reflect individual variation or factors not described in the registry record. No inferential comparison or uncertainty estimate is reported.
The study is designed to assess safety, tolerability, and pharmacological activity, with follow-up described as up to 5 years. The primary safety timeframe is through the primary completion visit, an average of 1 year. The available adverse event figures do not provide numerical results for the listed copper measures, ceruloplasmin activity, or responder status. Those results are not reported in the registry record.
These results also do not establish the duration or recurrence of events, the relationship of individual events to treatment, or how background therapy withdrawal may relate to outcomes. Those details are not reported in the registry record. The Drug-Induced Liver Injury term is listed at 50.0%, but the record does not provide enough denominator or event-level context to interpret it as a complete measure of risk.
Overall, the record offers a narrow descriptive account of adverse events in a small early-phase study. It cannot support a conclusion about comparative efficacy, comparative safety, or treatment benefit. The absence of a recorded death in these participants should not be generalized as proof that no risk exists.
13. Why This Trial Matters Statistically
Early-phase studies often generate the first structured observations about a treatment's safety and activity. This study is statistically notable for its combination of a single-dose escalation design, open-label assessment, and small enrollment. Those features mean that interpretation depends on distinguishing careful description of observed events from claims about comparative effects.
The registry records serious and other adverse event counts separately by dose cohort. Keeping those counts tied to their denominators helps readers see the limited amount of direct safety experience: each cohort has 2 participants listed at risk. This is important context for any listed percentage or apparent pattern. With so few observations, the counts are informative about what occurred in this study but provide little precision about event frequency beyond it.
The study also illustrates why a design label does not substitute for a reported analysis plan. The record calls the study adaptive and sequential, but does not describe the adaptation rules, dose-escalation decisions, missing-data methods, or multiplicity strategy. Those details matter for understanding how evidence was accumulated and how conclusions were intended to be drawn.
Finally, the registry distinguishes safety assessment from pharmacological outcomes by naming copper measures, ceruloplasmin activity, and responder status. Numerical results for those outcomes are not reported in the registry record. Recognizing the difference between listed outcomes and reported results helps keep interpretation aligned with the evidence actually recorded, without treating study objectives as findings.
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 limitation is the small enrollment of 4 participants, with only 2 participants listed at risk in each dose cohort. Such counts offer limited precision and make the observed pattern sensitive to individual experiences. The non-randomized, open-label design also prevents a controlled comparison between dose cohorts. The registry's own description warns that the arms are not a like-for-like control comparison.
The primary endpoint is described, but a complete numerical result by event category is not reported in the registry record. The posted safety counts do not include event-level detail such as timing beyond the stated onset-date summary approach, recurrence, duration, severity, or course. The denominator and additional context for the listed Drug-Induced Liver Injury percentage are not reported in the registry record.
Other specific limitations are the lack of reported numerical results for the named pharmacological outcomes and responder status, and the absence of reported confidence intervals, p-values, and analysis records. The registry record does not report how missing measurements were handled, the detailed membership rules for the Safety Analysis Set, multiplicity procedures, or the statistical analysis plan. It also does not report the rules for dose escalation or adaptation, a sample-size justification, or interim analysis details.
The registry lists follow-up of up to 5 years while defining the primary safety timeframe through the primary completion visit, an average of 1 year. The available adverse event counts do not characterize the full planned follow-up for each participant. These reporting limits mean that the recorded counts should be treated as a restricted description of the study experience, not as a complete assessment of longer-term safety or of the other named outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease — NCT04537377.
- Registry record last updated 2026-01-30; status last verified 2025-12.
- Results first posted 2026-01-28.
- 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.
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18. Record Summary
The registry describes NCT04537377, A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease, sponsored by Vivet Therapeutics SAS. It is a multicenter, non-randomized, open-label, adaptive, sequential, single-dose escalation study with 5-year follow-up. VTX-801 is administered intravenously to adults with Wilson's Disease, with safety, tolerability, and pharmacological activity assessed before and following withdrawal of background therapy.
Enrollment is 4. The study started on 2021-09-03, lists primary completion as 2024-12-17, and has status active, not recruiting. The primary outcome is the number of participants with safety events, including treatment-emergent adverse events, through the primary completion visit, an average of 1 year. The registry lists serious adverse event, other adverse event, and death counts by dose cohort, but does not report a comparative analysis or numerical results for the named pharmacological outcomes.