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

Primary Purpose

Congenital Cystic Kidney Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Venglustat GZ402671
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Cystic Kidney Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria :

  • Male or female adult with ADPKD who had completed the treatment period in Stage 1 or Stage 2 of Study EFC15392 (NCT03523728).
  • The participants who had an eGFR >30 mL/min/1.73 m^2:

    1. Measured at Visit 11 of the EFC15392 study for participant enrolled in the LTS15823 study at the time of Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.
    2. Measured at Screening visit for participant enrolled in the LTS15823 study not concomitantly to the Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.
  • Contraceptive used by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    1. Male participants who agreed to practice true abstinence in line with their preferred and usual lifestyle or to use double-contraceptive methods for the entire duration of the study and for at least 90 days following their last dose of IMP.
    2. Female participants who had a negative urine pregnancy test at the Baseline visit and agreed to practice true abstinence in line with their preferred and usual lifestyle or to use double contraceptive methods (including a highly effective method of contraception) for the entire duration of the study and for at least 6 weeks following their last dose of IMP.
  • Capable of giving signed informed consent before performance of any study related procedures not part of standard medical care.
  • Able to read, comprehend, and respond to the study questionnaires.

Exclusion criteria:

  • For participants who had lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study.
  • The participant had a new clinically significant, uncontrolled medical condition that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which would affect the efficacy or safety analysis if the condition exacerbated during the study, or that might significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
  • A history of drug abuse and/or alcohol abuse or alcohol dependence during the lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study when applicable.
  • Administration of tolvaptan or other polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screening visit (Visit 0) in the LTS15823 study when applicable.
  • The participant was currently receiving potentially cataractogenic medications, including a chronic regimen (more frequently than every 2 weeks) of any route of corticosteroids (including medium and high potency topical steroids), or any medication that may cause cataract, according to the Prescribing Information.
  • The participant had received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half lives, whichever was longer, prior to the Baseline visit (including consumption of grapefruit-containing products within 72 hours of starting venglustat administration).
  • Participation in another investigational interventional study or use of IMP, within 3 months or 5 half-lives, whichever was longer, before the Baseline visit (Visit 1) except participation in the EFC15392 study when applicable.
  • Liver enzymes (alanine aminotransferase /aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal unless the participant had the diagnosis of Gilbert syndrome. Participants with the Gilbert syndrome should had no additional symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level no more than 3 milligrams per decilitre (mg/dL) (51 micromoles per litre [μmol/L]) with conjugated bilirubin less than 20 percent (%) of the total bilirubin fraction.

For participants with or without lag phase between the end of EFC15392 study and entry into LTS15823 study:

  • The participant was pregnant or lactating.
  • Presence of severe depression as measured by BDI-II >28 at Visit 1 (for participants enrolled in the LTS15823 study at the time of the end of treatment visit of the EFC15392 study) or at Visit 0 (for participants enrolled in the LTS15823 study after the end-of-treatment visit of the EFC15392 study).
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sites / Locations

  • Investigational Site Number :8400019
  • Investigational Site Number :0360001
  • Investigational Site Number :0560002
  • Investigational Site Number :2760001
  • Investigational Site Number :3920001
  • Investigational Site Number :3920007
  • Investigational Site Number :3920002
  • Investigational Site Number :3920004
  • Investigational Site Number :4100002
  • Investigational Site Number :5280002
  • Investigational Site Number :7240003

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venglustat

Arm Description

Participants were to be treated with venglustat 15 milligrams once daily orally for 24 months or until venglustat was commercially available, whichever came first.

Outcomes

Primary Outcome Measures

Percent Change in Total Kidney Volume (TKV)
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

Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
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)
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
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
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.

Full Information

First Posted
January 8, 2021
Last Updated
October 3, 2022
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT04705051
Brief Title
Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
Acronym
STAGED-PKD-EXT
Official Title
Multicenter, Open-label, Extension Study to Characterize the Long-term Efficacy and Safety of Early Versus Delayed Treatment With Venglustat (GZ/SAR402671) in Patients at Risk of Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
LTS15823 (long-term extension of the EFC15392 study) was stopped after protocol specified interim analysis for futility of the parent EFC15392 study met the prespecified stopping rule based on the primary outcome measure.
Study Start Date
February 9, 2021 (Actual)
Primary Completion Date
July 13, 2021 (Actual)
Study Completion Date
July 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Cystic Kidney Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venglustat
Arm Type
Experimental
Arm Description
Participants were to be treated with venglustat 15 milligrams once daily orally for 24 months or until venglustat was commercially available, whichever came first.
Intervention Type
Drug
Intervention Name(s)
Venglustat GZ402671
Intervention Description
Pharmaceutical form: capsule Route of administration: oral
Primary Outcome Measure Information:
Title
Percent Change in Total Kidney Volume (TKV)
Description
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.
Time Frame
From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823
Secondary Outcome Measure Information:
Title
Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Description
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.
Time Frame
From the EFC15392 study Baseline to 24 months of open-label extension study LTS15823
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
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)
Title
Change From Baseline in Lens Clarity During the Open-label Extension Treatment-emergent Period of LTS15823 Study
Description
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.
Time Frame
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
Title
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
Description
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.
Time Frame
Baseline (EFC15392 study Baseline); from first IMP administration up to 3 months in study LTS15823, in comparison to the EFC15392 study Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria : Male or female adult with ADPKD who had completed the treatment period in Stage 1 or Stage 2 of Study EFC15392 (NCT03523728). The participants who had an eGFR >30 mL/min/1.73 m^2: Measured at Visit 11 of the EFC15392 study for participant enrolled in the LTS15823 study at the time of Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study. Measured at Screening visit for participant enrolled in the LTS15823 study not concomitantly to the Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study. Contraceptive used by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants who agreed to practice true abstinence in line with their preferred and usual lifestyle or to use double-contraceptive methods for the entire duration of the study and for at least 90 days following their last dose of IMP. Female participants who had a negative urine pregnancy test at the Baseline visit and agreed to practice true abstinence in line with their preferred and usual lifestyle or to use double contraceptive methods (including a highly effective method of contraception) for the entire duration of the study and for at least 6 weeks following their last dose of IMP. Capable of giving signed informed consent before performance of any study related procedures not part of standard medical care. Able to read, comprehend, and respond to the study questionnaires. Exclusion criteria: For participants who had lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study. The participant had a new clinically significant, uncontrolled medical condition that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which would affect the efficacy or safety analysis if the condition exacerbated during the study, or that might significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. A history of drug abuse and/or alcohol abuse or alcohol dependence during the lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study when applicable. Administration of tolvaptan or other polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screening visit (Visit 0) in the LTS15823 study when applicable. The participant was currently receiving potentially cataractogenic medications, including a chronic regimen (more frequently than every 2 weeks) of any route of corticosteroids (including medium and high potency topical steroids), or any medication that may cause cataract, according to the Prescribing Information. The participant had received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half lives, whichever was longer, prior to the Baseline visit (including consumption of grapefruit-containing products within 72 hours of starting venglustat administration). Participation in another investigational interventional study or use of IMP, within 3 months or 5 half-lives, whichever was longer, before the Baseline visit (Visit 1) except participation in the EFC15392 study when applicable. Liver enzymes (alanine aminotransferase /aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal unless the participant had the diagnosis of Gilbert syndrome. Participants with the Gilbert syndrome should had no additional symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level no more than 3 milligrams per decilitre (mg/dL) (51 micromoles per litre [μmol/L]) with conjugated bilirubin less than 20 percent (%) of the total bilirubin fraction. For participants with or without lag phase between the end of EFC15392 study and entry into LTS15823 study: The participant was pregnant or lactating. Presence of severe depression as measured by BDI-II >28 at Visit 1 (for participants enrolled in the LTS15823 study at the time of the end of treatment visit of the EFC15392 study) or at Visit 0 (for participants enrolled in the LTS15823 study after the end-of-treatment visit of the EFC15392 study). Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :8400019
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506-9180
Country
United States
Facility Name
Investigational Site Number :0360001
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Investigational Site Number :0560002
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number :2760001
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Investigational Site Number :3920001
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Investigational Site Number :3920007
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Investigational Site Number :3920002
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Investigational Site Number :3920004
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Investigational Site Number :4100002
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Name
Investigational Site Number :5280002
City
Nijmegen
ZIP/Postal Code
6525GA
Country
Netherlands
Facility Name
Investigational Site Number :7240003
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08003
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Learn more about this trial

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

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