Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat (NCT04705051), a na phase 3 study. The primary outcome is Percent Change in Total Kidney Volume (TKV).

2. Clinical Question

The clinical question was whether early versus delayed treatment with venglustat affected total kidney volume (TKV) in participants at risk of rapidly progressive autosomal dominant polycystic kidney disease (ADPKD). The stated primary objective was to determine the effect of treatment timing on TKV. The study also set out to assess estimated glomerular filtration rate (eGFR), safety, lens clarity and mood.

The treatment under study was venglustat, planned at 15 milligrams once daily by mouth for 24 months or until it became commercially available, whichever came first. The record identifies this as a multicenter, open-label extension study. It lists a single-group model and one Venglustat treatment group; it does not describe a like-for-like control comparison in this extension record. The record therefore establishes the intended early-versus-delayed question, but does not provide a randomized comparison of those strategies for this study.

The primary endpoint was percent change in TKV from the baseline of parent study EFC15392 to 24 months of the extension study, LTS15823. TKV is used as a measure of ADPKD disease progression. However, the extension was terminated early after the sponsor terminated the parent study following its planned prespecified futility analysis. The registry states that efficacy analysis was not performed in the extension because of early termination and low enrollment. Consequently, the registry record does not report an estimate of the effect of early versus delayed treatment on TKV.

These distinctions matter: an objective states what a study intended to investigate, while an analyzed endpoint requires sufficient collected data and a reported analysis. The intended question is identifiable, but the posted extension results do not answer it.

3. Trial Design

LTS15823 was registered as a Phase 3, multicenter, open-label extension study. The registry lists a single-group model, no masking, and enrollment of 24. It identifies Sanofi as the sponsor. The listed condition is congenital cystic kidney disease, and the study title and objectives specify autosomal dominant polycystic kidney disease.

The intervention was venglustat. Participants were to receive 15 milligrams once daily orally for 24 months or until venglustat became commercially available, whichever came first. The extension was intended to characterize long-term efficacy and safety and to address early versus delayed treatment. However, the registry’s design fields identify a single group, and its record does not describe randomized allocation to an early-treatment group and a delayed-treatment control group. The record also cautions that this was not a randomized comparison and that the arms are not a like-for-like control comparison. It would therefore be inappropriate to interpret the extension as a conventional randomized controlled trial comparing treatment timing.

The study began on 2021-02-09, had a primary completion date of 2021-07-13, and is listed as terminated. The registry explains that LTS15823 was terminated prematurely after the sponsor decided to terminate parent study EFC15392 (NCT03523728). The parent-study decision followed a planned prespecified futility analysis. The registry attributes that decision to a lack of efficacy in the ADPKD population, not to safety findings with venglustat.

Only 2 participants reached the planned Month 3 visit, and the record describes very limited post-baseline data. It states that the extension analysis was limited to available safety and tolerability data. Thus, the design describes the intended long-term investigation, while the termination and limited follow-up define what could actually be analyzed.

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 at risk of rapidly progressive autosomal dominant polycystic kidney disease (ADPKD) who had previously completed Stage 1 of Study EFC15392 (NCT: NCT03523728) were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: For study LTS15823, due to low number of enrollments as compared to the planned numbers and very limited data available post-baseline (only 2 participants reached the planned Month 3 visit), the analysis was carried out only on the available safety and tolerability data. Due to early termination of the study, no efficacy data was available at Month 24 hence the efficacy analysis was not performed.

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 enrolled population which included all participants allocated to an intervention kit by interactive response technology (IRT) regardless of whether the intervention was received or not.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Total Kidney Volume (TKV), measured over From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823.

The primary endpoint was percent change in total kidney volume (TKV), measured from the baseline of parent study EFC15392 to 24 months of open-label extension study LTS15823. The registry describes TKV as a measure of disease progression in participants with ADPKD. Tracking change in kidney volume over time was intended to characterize the effect of early versus delayed treatment with venglustat.

Percent change expresses an endpoint as change relative to its starting value. In general, this can make change easier to interpret across participants whose baseline measurements differ. The registry record does not report the endpoint’s units, a numerical estimate, a measure of variability, or a confidence interval. It also states directly that an efficacy analysis was not performed because the study ended early and enrollment was low. Therefore, no percent-change result for TKV can be interpreted from the posted extension results.

The planned timeframe is important to interpretation. The primary endpoint referred to a 24-month extension assessment, but only 2 participants reached the planned Month 3 visit. The available follow-up described in the record was therefore very limited relative to the endpoint’s intended time horizon. The endpoint remains a stated study objective, not an observed efficacy finding from this extension.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation of this record starts with distinguishing the intended question from the analysis that was completed. The stated primary objective concerned the effect of early versus delayed venglustat treatment on total kidney volume. The registry’s design fields identify a single-group, open-label extension, and the record warns that this is not a randomized comparison. Most importantly, it says the efficacy analysis was not performed. There is therefore no TKV effect estimate in the extension results to interpret.

What does an endpoint estimate represent?

In general, an endpoint estimate is a numerical summary of the outcome observed under a defined analysis. For a change endpoint, the summary depends on which participants have usable measurements at the relevant timepoints and on how the analysis handles incomplete observations. Here, the stated endpoint was percent change in TKV from the parent-study baseline to 24 months of extension. The record reports neither the endpoint estimate nor the analysis details required to reconstruct one. Any numerical TKV result would therefore go beyond what the registry record reports.

The record notes that only 2 participants reached the planned Month 3 visit and that very limited post-baseline data were available. This matters because an endpoint tied to a later visit needs relevant follow-up data. Without sufficient data and a performed efficacy analysis, there is no basis for describing the observed size or precision of change in TKV. The intended 24-month timeframe is not the same as evidence that participants were followed to that point.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the methods used to calculate it. A narrow interval usually indicates greater statistical precision than a wide interval, while both the estimate and the interval depend on the analysis population and assumptions. No confidence interval for the primary endpoint is reported in the registry record. It is therefore not possible to assess the precision of a TKV effect estimate from these results.

Likewise, no extension-study efficacy test or p-value is reported. A statistical test, when used, evaluates compatibility between observed data and a specified null model; it does not by itself measure clinical importance. Here, the absence of a test is a consequence of the reported absence of an efficacy analysis, not a reported nonsignificant finding. No conclusion should be drawn that an unreported test failed to reach a threshold.

Why does the design affect interpretation?

In general, random allocation can help make treatment groups comparable at the start of a study, while a concurrent control can help separate treatment differences from changes that might occur over time or for other reasons. This extension is listed as single-group, with no masking, and the registry cautions against treating its arms as a like-for-like control comparison. The record does not support interpreting the extension as a randomized comparison of early and delayed treatment. Even if a within-group change had been reported, it would not by itself establish that treatment timing caused the change.

The extension’s open-label status means treatment was not masked. In general, knowledge of assigned treatment can influence reporting or assessment for outcomes that involve judgment. TKV is a volume measure, but the registry record does not report the measurement procedures or assessor masking. Those details should not be inferred.

How should the safety counts be understood?

The record reports 23 participants at risk for serious adverse events and 1 affected in the Venglustat 15mg group; it reports 23 at risk and 0 affected for other adverse events, and 0 deaths. These are descriptive counts. They do not constitute a comparative estimate of excess or reduced risk, since the registry does not report a randomized control group for this extension. Wound Infection is listed among serious adverse event terms at 4.3%. The record does not provide enough detail to use that term as a comparative safety estimate.

The planned prespecified futility analysis belongs to the parent study EFC15392. The registry says the parent study was terminated following its results, but it does not report the futility analysis methods, threshold, estimate, or numerical result in this extension record. General explanations of futility analyses cannot fill that gap: in general, such analyses assess whether continued study is likely to meet a specified objective, but the particular procedure used for the parent study is not reported.

Finally, any sample-size planning illustration must be kept separate from observed trial evidence. In general, a planning calculation uses assumptions about an effect, variability, significance level, and allocation to estimate a required sample size; it is not a measure of power achieved by participants who enrolled. The registry record does not report the extension’s own sample-size justification or a numerical efficacy analysis. It also does not report a basis for treating any planning illustration as observed power. The enrollment of 24 is a registry fact, not an efficacy estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary objectives: eGFR assessed using the CKD-EPI equation, treatment-emergent adverse events and serious adverse events, lens clarity, and mood measured with the Beck Depression Inventory-II (BDI-II). These outcomes cover different domains and use different measurements. The record does not report how statistical testing across multiple endpoints was handled.

In general, testing several outcomes can increase the chance of at least one apparently notable result arising by chance if tests are interpreted without accounting for multiplicity. Statistical plans may address this through a prespecified hierarchy, adjustment, or other strategy. The registry record does not report whether any such strategy was planned for LTS15823, nor does it report an analysis plan or inferential results for these secondary outcomes. No adjustment method or testing order should be inferred.

Missing-data handling is also not reported in the registry record. The record says only 2 participants reached the planned Month 3 visit and that post-baseline information was very limited. It does not describe how incomplete measurements would have been handled for TKV, eGFR, lens clarity, or mood, or how participants would have been included in efficacy analysis populations. Since the primary efficacy analysis was not performed, there is no reported method for addressing missing endpoint measurements in that analysis.

In general, missing data can affect both the amount of information available and the interpretation of an estimate. The consequences depend on why data are missing and on the assumptions and methods used to handle them. Those reasons and methods are not reported for the extension. The registry does not support a claim that missingness was random, that any imputation was used, or that a particular analysis population was defined. The parent study’s futility analysis does not fill these gaps about the extension’s own multiplicity, missing-data, or analysis-population procedures.

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

Serious events with the highest arm-level rate: wound infection (4.3%).

The registry reports safety information for the Venglustat 15mg group. It lists 23 participants at risk for serious adverse events, with 1 participant affected. For other adverse events, it lists 23 at risk and 0 affected. Deaths are reported as 0. Wound Infection is listed among the serious adverse event terms at 4.3%.

These figures are descriptive. The record does not present a randomized control group for a like-for-like safety comparison, so the counts do not estimate how safety outcomes would differ under another treatment strategy. They should also be kept distinct from the sponsor’s reason for ending the study: the registry says the parent-study termination followed a futility analysis and was due to a lack of efficacy in the ADPKD population, not safety findings with venglustat.

In general, adverse-event counts depend on the period of observation and the definitions used to classify events. The registry record gives the group’s at-risk counts but does not provide additional detail about event timing, exposure-adjusted rates, or a comparative analysis. The 4.3% listing for Wound Infection should therefore be read as a reported term, not as evidence of a comparative treatment effect. No safety conclusion beyond the posted descriptive information is warranted.

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

The results mean that the extension did not produce a reported efficacy analysis of its primary TKV endpoint. The registry states that the study ended early, enrollment was low, post-baseline data were very limited, and only 2 participants reached the planned Month 3 visit. It reports that analysis was carried out only on available safety and tolerability data. The planned TKV outcome was percent change from parent-study baseline to 24 months, but no numerical change or uncertainty estimate is reported.

This does not mean that TKV did not change, that early and delayed treatment had identical effects, or that the treatment had a particular effect size. It means the extension record does not report an efficacy analysis capable of answering those questions. A missing result is not a result of no effect. Nor should the parent study’s futility decision be presented as an extension-study TKV estimate. The registry attributes that decision to the parent study’s planned prespecified futility analysis and says it was due to lack of efficacy in the ADPKD population, not safety findings with venglustat.

The safety information is similarly limited in what it can establish. The registry reports 1 participant affected by serious adverse events among 23 at risk, 0 affected by other adverse events among 23 at risk, and 0 deaths. Wound Infection is listed at 4.3% among serious adverse event terms. These are descriptive findings from the reported group, not comparative evidence against another treatment.

The extension’s single-group designation and absence of a like-for-like control comparison further limit causal interpretation. In general, observing outcomes in one group does not isolate treatment effects from other explanations for change over time. The registry does not provide a randomized comparison of early versus delayed treatment in this extension. The appropriate conclusion is therefore about the limits of the available evidence: the intended efficacy question is documented, but the extension results do not answer it quantitatively.

13. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a planned endpoint and an analyzed endpoint. The registry specifies a clinically relevant measurement, percent change in TKV, and an intended 24-month timeframe. But because the extension ended early and had very limited post-baseline information, the planned efficacy analysis was not performed. A clearly stated objective is not itself a result.

It also shows why enrollment, follow-up, and analysis must be considered together. The registry lists enrollment of 24, yet only 2 participants reached the planned Month 3 visit. Enrollment alone does not establish that enough outcome information was collected to estimate an endpoint or its precision. When follow-up is limited, a numerical efficacy claim may not be supported even if the endpoint and assessment time are specified.

The record also emphasizes the distinction between a single-group extension and a randomized comparison. The stated question concerned early versus delayed treatment, but the extension is listed as single-group, and the registry cautions that the arms are not a like-for-like control comparison. In general, design determines which comparisons can be interpreted causally; objectives alone cannot create a valid control contrast.

Finally, the study’s termination context must be assigned to the correct study. The sponsor terminated the extension following the decision to terminate the parent study, which was based on a planned prespecified futility analysis. The record says that rationale concerned lack of efficacy in the ADPKD population and was not linked to safety findings with venglustat. This is important context, but it does not replace the missing extension efficacy analysis or provide its numerical result. Careful statistical reporting keeps these related details distinct.

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 that the registry reports no efficacy analysis for the primary endpoint. The endpoint was intended to measure percent change in TKV from the parent-study baseline to 24 months, but the record says the extension ended early and enrollment was low. Only 2 participants reached the planned Month 3 visit, and the available post-baseline data were described as very limited. No endpoint estimate, uncertainty interval, or statistical test is reported.

The study is listed as open-label and single-group, and the record cautions that it is not a randomized comparison with like-for-like control arms. The objective concerned early versus delayed treatment, but the design information does not support reading the extension as a randomized test of that contrast. The registry does not report details that would establish a controlled comparison in this extension.

The available information also does not describe the extension’s statistical analysis plan, missing-data methods, multiplicity strategy, or efficacy analysis populations. Measurement procedures for TKV and the handling of incomplete endpoint observations are not reported in the registry record. These omissions prevent assessment of how an efficacy analysis would have been specified or how its precision might have been evaluated.

The safety results are descriptive and lack a like-for-like control comparison. The record lists at-risk and affected counts and a serious adverse event term, but does not report comparative safety estimates. The parent-study futility decision provides termination context, not a substitute for the extension’s unperformed endpoint analysis. These limitations restrict interpretation to the study’s intent, termination, and reported safety and tolerability information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat — NCT04705051.
• Registry record last updated 2025-09-17; status last verified 2025-09.
• Results first posted 2022-10-06.
• 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

NCT04705051 is a Phase 3, multicenter, open-label extension study of venglustat in participants at risk of rapidly progressive ADPKD. The registry lists a single-group model, enrollment of 24, and Sanofi as sponsor. The planned regimen was venglustat 15 milligrams once daily orally for 24 months or until commercial availability, whichever came first.

The primary endpoint was percent change in TKV from the parent-study baseline to 24 months. Secondary outcomes concerned eGFR, adverse events, lens clarity, and mood. The study began on 2021-02-09, had a primary completion date of 2021-07-13, and is listed as terminated.

The registry says the extension was terminated after the sponsor terminated parent study EFC15392 following its planned prespecified futility analysis. The parent-study decision was attributed to lack of efficacy in the ADPKD population, not safety findings. Because of early termination and low enrollment, the extension’s efficacy analysis was not performed; only available safety and tolerability data were analyzed. The record reports 1 participant affected by serious adverse events among 23 at risk, 0 affected by other adverse events among 23 at risk, and 0 deaths.