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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)

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

24

A total of 24 participants were enrolled in the study, of which 23 (95.8%) participants were treated. All the participants who were treated discontinued the study treatment permanently. The reason for study treatment discontinuation in all participants was due to the termination of the preceding Study EFC15392. Study EFC15392 was terminated by the sponsor based on the results of the futility analysis. Overall, the mean (standard deviation [SD]) age was 45.3 (4.7) years. All participants were either White or Asian (12 [50%] participants, each). A total of 15 (62.5%) enrolled participants were male and 9 (37.5%) participants were female. No participants were Hispanic or Latino and the mean (SD) body mass index was 26.4 (4.9) kg/m^2.

Enrolled: 24 participants Treated: 23 participants Completed: 0 participants Discontinued: 24 participants

Two (8.7%) participants had treatment-emergent adverse event(TEAE) during the study. One of these participants had a serious TEAE of wound infection, and the other had a TEAE of thirst. The wound infection for which the participant was hospitalized was reported as not resolved and considered not related to IMP by the Investigator. No participant had a TEAE leading to death or permanent treatment discontinuation, a treatment-emergent AESI, or an IMP-related TEAE.

Efficacy was not assessed due to early termination of the study.

Overall, the safety analysis did not identify any new emerging safety issues compared to other studies conducted with venglustat. No study treatment-related deaths were reported in this study. This study was terminated prematurely by the Sponsor following a decision to terminate the parent study EFC15392 based on the results of the futility analysis performed for this study. Termination decision was due to a lack of efficacy in the ADPKD patient population and not linked to safety findings with venglustat.

Dec. 21, 2022

No

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

https://jrct.mhlw.go.jp/latest-detail/jRCT2031200348

Tanaka Tomoyuki

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Complete

Feb. 09, 2021

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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.

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 micro mol/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.

Both

Congenital cystic kidney disease

Drug: Venglustat (GZ402671)
Pharmaceutical form: capsule, Route of administration: oral

Percent change in TKV [Time frame for evaluation: From the EFC15392 study baseline to 24 months of open-label extension study]
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

1. Change in eGFR [Time frame for evaluation:From the EFC15392 study baseline to 24 months of open-label extension study]
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 [Time frame for evaluation:From 1st treatment intake to last treatment of open-label extension study + 30 days]

3. Change in lens clarity [Time frame for evaluation: From EFC15392 study baseline to last treatment of open-label extension study +30 days]
Change from EFC15392 study baseline in the lens clarity by ophthalmological examination during the open label extension treatmentemergent period

4. Change in score of Beck Depression Inventory-II (BDI-II) [Time frame for evaluation: From EFC15392 study baseline to last treatment of open-label extension study +30 days]
Change from EFC15392 study baseline in BDI II score during the open-label extension treatment emergent period

+81-3-5802-1584

Dec. 22, 2020

United States/Australia/Australia/Germany/Republic of Korea/Netherlands/Spain