Long-term treatment of autosomal dominant polycystic kidney disease (ADPKD) with venglustat

• Register: EUCTR
• Last refreshed on: 7 February 2022
• Main ID: EUCTR2020-004400-34-DE
• Date of registration: 25/02/2021
• Prospective Registration: Yes
• Primary sponsor: Sanofi-Aventis Recherche & Développement
• Public title: Long-term treatment of autosomal dominant polycystic kidney disease (ADPKD) with venglustat
• Scientific 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) - STAGED-PKD-EXT
• Date of first enrolment: 23/03/2021
• Target sample size: 640
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004400-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: single group If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Israel, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Spain, Taiwan, Turkey, United Kingdom

Contacts

• Affiliation: Sanofi-Aventis Deutschland GmbH

• Affiliation: Sanofi-Aventis Deutschland GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female adult with ADPKD who has completed the treatment period in Stage 1 or Stage 2 of Study EFC15392.

- The patient has an eGFR >30 mL/min/1.73 m2:
a) 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.
b) 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 use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a) Male participants must agree 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.
b) Female participants must have a negative urine pregnancy test at the Baseline visit and agree 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 640
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Participants are excluded from the study if any of the following criteria apply:

For participants who have lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study:
-The patient has a new clinically significant, uncontrolled medical condition that, in the opinion of the Investigator, would put the safety of the patient at risk through participation, or which would affect the efficacy or safety analysis if the condition exacerbated during the study, or that may 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 patient is 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 patient has received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half lives, whichever is 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 is 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 patient has the diagnosis of Gilbert syndrome. Patients with the Gilbert syndrome should have no additional symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level no more than 3 mg/dL (51 µmol/L) with conjugated bilirubin less than 20% of the total bilirubin fraction.


For participants with or without lag phase between the end of EFC15392 study and entry into LTS15823 study:
-The patient is pregnant or lactating.
-Presence of severe depression as measured by Beck Depression Inventory 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Congenital cystic kidney disease
MedDRA version: 20.0 Level: PT Classification code 10010428 Term: Congenital cystic kidney disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Capsule
INN or Proposed INN: venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ/SAR402671
Other descriptive name: GZ/SAR402671
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From the EFC15392 study baseline to 24 months of open-label extension study

Main 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 ADPKD.

Secondary Objective: - To determine the effect of early versus delayed treatment with venglustat on the renal function (estimated glomerular filtration rate [eGFR]).

- 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).

Primary end point(s): Percent change in TKV: Percent change in TKV based on magnetic resonance imaging (MRI) from the EFC15392 study baseline to 24 months of open-label extension study, in early treated and delayed-treated participants

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1: From the EFC15392 study baseline to 24 months of open-label extension study

2: From 1st treatment intake to last treatment of open-label extension study + 30 days

3,4: From EFC15392 study baseline to last treatment of open-label extension study + 30 days

Secondary end point(s): 1 - Change in eGFR: Change in eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) from the EFC15392 study baseline to 24 months of open label extension study, in early treated and delayed-treated participants

2 - Number of adverse events

3 - Change in lens clarity: Change from EFC15392 study baseline in the lens clarity by ophthalmological examination during the open label extension treatment-emergent period

4 - Change in score of Beck Depression Inventory- II (BDI-II): Change from EFC15392 study baseline in BDI II score during the open-label extension treatment emergent period

Secondary ID(s)

2020-004400-34-NL

LTS15823

Source(s) of Monetary Support

Sanofi-Aventis Recherche & Développement

Ethics review

Status: Approved
Approval date: 23/03/2021
Contact: