Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
- Registration Number
- NCT04705051
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
-To determine the effect of early versus delayed treatment with venglustat on the total kidney volume (TKV) in participants at risk of rapidly progressive autosomal dominant polycystic kidney disease (ADPKD).
Secondary Objective:
* To determine the effect of early versus delayed treatment with venglustat on the renal function (estimated glomerular filtration rate \[eGFR\] \[Chronic Kidney Disease Epidemiology Collaboration {CKD-EPI} equation\]).
* To characterize the safety profile of venglustat.
* To evaluate the effect of venglustat on the lens by ophthalmological examination.
* To evaluate the effect of venglustat on mood using Beck Depression Inventory-II (BDI-II).
- Detailed Description
The planned study duration per participant was 25.5 months (maximal). Screening period (when applicable): up to 2 weeks. Core treatment period: 24 months. Follow-up: 30 days after final dose of the investigational medicinal product (IMP) (venglustat).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Venglustat Venglustat GZ402671 Participants were to be treated with venglustat 15 milligrams once daily orally for 24 months or until venglustat was commercially available, whichever came first.
- Primary Outcome Measures
Name Time Method Percent Change in Total Kidney Volume (TKV) From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823 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.
- Secondary Outcome Measures
Name Time Method Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) 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) 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.
Change From Baseline in Lens Clarity During the Open-label Extension Treatment-emergent Period of LTS15823 Study 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 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.
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 (EFC15392 study Baseline); from first IMP administration up to 3 months in study LTS15823, in comparison to the EFC15392 study Baseline 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.
Trial Locations
- Locations (11)
Investigational Site Number :5280002
🇳🇱Nijmegen, Netherlands
Investigational Site Number :3920007
🇯🇵Osaka-shi, Osaka, Japan
Investigational Site Number :3920002
🇯🇵Bunkyo-ku, Tokyo, Japan
Investigational Site Number :2760001
🇩🇪Berlin, Germany
Investigational Site Number :0560002
🇧🇪Leuven, Belgium
Investigational Site Number :3920001
🇯🇵Sapporo-shi, Hokkaido, Japan
Investigational Site Number :4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :7240003
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :3920004
🇯🇵Shinjuku-ku, Tokyo, Japan
Investigational Site Number :0360001
🇦🇺Westmead, New South Wales, Australia
Investigational Site Number :8400019
🇺🇸Morgantown, West Virginia, United States