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

NCT04705051 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: LTS158232020-004400-34U1111-1256-8805
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 11

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).

Conditions

Congenital Cystic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (4)

• 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

• 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)

• 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

• 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

Study Arms (1)

Venglustat

EXPERIMENTAL

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

Drug: Venglustat GZ402671

Interventions

Venglustat GZ402671 DRUG

Pharmaceutical form: capsule Route of administration: oral

Venglustat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (11)

Investigational Site Number :8400019

Morgantown, West Virginia, 26506-9180, United States

Location

Investigational Site Number :0360001

Westmead, New South Wales, 2145, Australia

Location

Investigational Site Number :0560002

Leuven, 3000, Belgium

Location

Investigational Site Number :2760001

Berlin, 10117, Germany

Location

Investigational Site Number :3920001

Sapporo, Hokkaido, 060-8648, Japan

Location

Investigational Site Number :3920007

Osaka, Osaka, 545-8586, Japan

Location

Investigational Site Number :3920002

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

Investigational Site Number :3920004

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Investigational Site Number :5280002

Nijmegen, 6525GA, Netherlands

Location

Investigational Site Number :4100002

Seoul, Seoul-teukbyeolsi, 07061, South Korea

Location

Investigational Site Number :7240003

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Related Links

• LTS15823 Plain Language Results Summary

MeSH Terms

Conditions

Kidney Diseases, Cystic

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

The study was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392. Termination decision was due to lack of efficacy in ADPKD population and not linked to safety findings with venglustat.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 12, 2021
• Study Start: February 9, 2021
• Primary Completion: July 13, 2021
• Study Completion: July 13, 2021
• Last Updated: September 17, 2025
• Results First Posted: October 6, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

KR (1); NL (1); AU (1); US (1); JP (4); ES (1); DE (1); BE (1)