Trial Outcomes & Findings for Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat (NCT NCT04705051)

Results Overview

Total kidney volume is a measure of disease progression in the ADPKD participants. Study LTS15823 was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392 (NCT03523728). Study EFC15392 was terminated based on the results of the planned prespecified futility analysis performed for this study. Termination decision was due to a lack of efficacy in the ADPKD population and not linked to safety findings with venglustat. Due to the early termination of study LTS15823 and low enrollment numbers, efficacy analysis was not performed.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

24 participants

Primary outcome timeframe

From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823

Results posted on

2025-09-17

Participant Flow

The study was conducted at 11 centers in 8 countries. A total of 24 participants were enrolled in the study between 09 February 2021 and 13 July 2021. Out of which, 23 participants were treated.

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.

Participant milestones

Participant milestones
Measure	Venglustat 15mg Participants received open-label treatment with Venglustat 15 milligrams (mg) once daily orally up to a maximum of 16 weeks.
Overall Study STARTED	24
Overall Study Treated	23
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Venglustat 15mg Participants received open-label treatment with Venglustat 15 milligrams (mg) once daily orally up to a maximum of 16 weeks.
Overall Study Enrolled but not treated	1
Overall Study Study terminated by sponsor	23

Baseline Characteristics

Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Venglustat 15mg n=24 Participants Participants enrolled in open-label Venglustat 15 mg once daily orally.
Age, Continuous	45.3 years STANDARD_DEVIATION 4.7 • n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	15 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	12 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	12 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823

Population: 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.

Total kidney volume is a measure of disease progression in the ADPKD participants. Study LTS15823 was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392 (NCT03523728). Study EFC15392 was terminated based on the results of the planned prespecified futility analysis performed for this study. Termination decision was due to a lack of efficacy in the ADPKD population and not linked to safety findings with venglustat. Due to the early termination of study LTS15823 and low enrollment numbers, efficacy analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823

Population: 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.

eGFR is a measure of kidney function assessed through blood/serum. Study LTS15823 was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392 (NCT03523728). Study EFC15392 was terminated based on the results of the planned prespecified futility analysis performed for this study. Termination decision was due to a lack of efficacy in the ADPKD population and not linked to safety findings with venglustat. Due to the early termination of study LTS15823 and low enrollment numbers, efficacy analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first administration of the IMP in LTS15823 study up to the last IMP administration in LTS15823 study + 30 days (i.e., up to approximately 20 weeks)

Population: Analysis was performed on Long-term extension safety population which included all participants who had received at least one dose of study medication.

Adverse event (AE) was defined as any untoward medical occurrence in participant who received investigational medicinal product (IMP) and did not necessarily have a causal relationship with treatment. All reported AEs were TEAEs that developed/worsened during 'TEAE period' (defined as the time from the first administration of the IMP in LTS15823 study up to the last IMP administration + 30 days). A SAEs was defined as any AE that at any dose results in: death; is life threatening; requires initial or prolonged inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via an authorized medicinal product; is a medically important event.

Outcome measures

Outcome measures
Measure	Venglustat 15mg n=23 Participants Participants enrolled in open-label Venglustat 15 mg once daily orally.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAEs	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	1 Participants

SECONDARY outcome

Timeframe: Baseline (EFC15392 study Baseline); from first administration of IMP up to last administration of IMP of open-label extension study LTS15823 + 30 days (i.e., up to approximately 20 weeks), in comparison to the EFC15392 study Baseline

Population: For study LTS15823, due to early termination of the study, no ophthalmological data was collected at the planned visits as per protocol and thus the planned analysis was not performed.

Change from EFC15392 study Baseline in the lens clarity was assessed by ophthalmological examination with World Health Organization (WHO) simplified cataract grading system during the open label extension treatment-emergent period of LTS15823 study. Study LTS15823 was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392 (NCT03523728). Study EFC15392 was terminated based on the results of the planned prespecified futility analysis performed for this study. Termination decision was due to a lack of efficacy in the ADPKD population and not linked to safety findings with venglustat. Baseline was defined as the values from EFC15392 study Baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (EFC15392 study Baseline); from first IMP administration up to 3 months in study LTS15823, in comparison to the EFC15392 study Baseline

Population: Analysis was performed on long-term extension safety population. BDI score was collected for 16 participants at Baseline and up to 3 months at the end of trial visit i.e., within 30 days after last dose of study drug following the decision for early termination of the study. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

BDI-II was a validated self-reported instrument of 21 questions which were each scored on a Likert scale of 0 to 3. Total score was calculated as sum of all scores of 21 questions. Total scores ranged from 0 (minimal depression) to 63 (severe depression), with higher score totals indicating more severe depression symptoms (0 to 13: indicates minimal depression;14 to 19: indicates mild depression; 20 to 28: indicates moderate depression; and 29 to 63: indicates severe depression). A negative change from baseline indicated an improvement. Baseline was defined as the values from EFC15392 study Baseline.

Outcome measures

Outcome measures
Measure	Venglustat 15mg n=16 Participants Participants enrolled in open-label Venglustat 15 mg once daily orally.
Effect on Mood With Change From Baseline in Beck Depression Inventory (BDI-II) Score During the Open-label Extension Treatment-emergent Period of LTS15823 Study Baseline	2.188 score on a scale Standard Deviation 4.086
Effect on Mood With Change From Baseline in Beck Depression Inventory (BDI-II) Score During the Open-label Extension Treatment-emergent Period of LTS15823 Study Change from Baseline	-0.875 score on a scale Standard Deviation 4.455

Adverse Events

Venglustat 15mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Venglustat 15mg n=23 participants at risk Participants received open-label treatment with Venglustat 15 mg once daily orally up to a maximum of 16 weeks.
Infections and infestations Wound Infection	4.3% 1/23 • Number of events 1 • From the first administration of the IMP in LTS15823 study up to the last IMP administration in LTS15823 study + 30 days (i.e., up to approximately 20 weeks) Reported AEs were TEAEs i.e., AEs that developed/worsened during the 'TEAE period'. Analysis was performed on long-term extension safety population.

Other adverse events

Adverse event data not reported

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER