A Medical Research Study Designed to Determine if Venglustat can be a Future Treatment for ADPKD Patients

• Register: EUCTR
• Last refreshed on: 3 November 2021
• Main ID: EUCTR2017-004084-12-PT
• Date of registration: 11/06/2018
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: A Medical Research Study Designed to Determine if Venglustat can be a Future Treatment for ADPKD Patients
• Scientific title: Multicenter, Randomized, Double-blind, Placebo-controlled Two Stage Study to Characterize the Efficacy, Safety, Tolerability and Pharmacokinetics of GZ/SAR402671 in Patients at risk of Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD) - STAGED-PKD
• Date of first enrolment: 06/08/2018
• Target sample size: 982
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004084-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, China, Czech Republic, Czechia, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Romania, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Cristina Garcia
• Affiliation: Sanofi Produtos Farmacêuticos, Lda

• Name: Cristina Garcia
• Affiliation: Sanofi Produtos Farmacêuticos, Lda

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female adult with ADPKD with age at the time the consent is signed:
a) between 18 to 50 years (both inclusive) for patients from Stage 1
b) between 18 to 50 years (both inclusive) for patients from Stage 2
with eGFR between 45 and 89.9 mL/min/1.73 m2 during screening period*
c) between 18 to 55 years (both inclusive) for patients from Stage 2 with eGFR between 30 and 44.9 mL/min/1.73 m2 during screening period* Diagnosis of ADPKD in patients with a family history, will be based on unified Pei criteria.
In the absence of a family history, the diagnosis will be based on the presence of renal cysts bilaterally, totaling at least 20, in the absence of findings suggestive of other cystic renal diseases.
- Mayo Imaging Classification of ADPKD Class 1C, 1D or 1E**.
** TKV volume must be confirmed by a central reader prior to Visit 3
- Estimated glomerular filtration rate between 45 to 89.9 mL/min/1.73 m2 during screening period* (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] for Stage 1.
Estimated glomerular filtration rate between 30 to 89.9 mL/min/1.73 m2 during screening period* (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) for Stage 2.
*Eligibility will be confirmed by eGFR value from one of the two first pre-randomization eGFR measurements.
-Stable treatment regimen of antihypertensive therapy for at least 30 days prior to screening visit for hypertensive patient.
-Able to read, comprehend and respond to the study questionnaires.
-Patient has given voluntary written informed consent before performance of any study related procedures not part of standard medical care.
- Patient does not have access to tolvaptan at the time of study start or tolvaptan is not indicated for treatment of patient according to treating physician (patient does not meet recommended criteria for treatment, refuses to initiate or does not tolerate treatment with tolvaptan).
-The patient, if female of childbearing potential, must have a negative blood pregnancy test [beta human chorionic gonadotropin (ß-hCG)] at the screening visit and a negative urine pregnancy test at the baseline visit.
- Female patients of childbearing potential and male patients must 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 female participants of childbearing potential) for the entire duration of the study and for at least 6 weeks for females and 90 days for males following their last dose of study drug.
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 982
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Systolic blood pressure >160 mm Hg at Run-in and Baseline visits.
-Administration within 3 months prior to the screening visit of tolvaptan or other Polycystic Kidney Disease-modifying agents (somatostatin analogues).
-Current participation in another investigational interventional study or use of investigational medicinal product (IMP), within 3 months or 5 half lives, whichever is longer, before randomization.
- The patient has a positive result of any of the following tests: hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti HIV1 and anti HIV2 Ab). Patients with a positive hepatitis B surface antibody (HBsAb) test are eligible if other criteria are met (ie, negative tests for: HBsAg, hepatitis B core antibody [HBcAb]). Patients immune due to natural infection (positive hepatitis B surface antibody (HBsAb), negative hepatitis B surface antigen (HBsAg) and positive hepatitis B core antibody [HBcAb]) are eligible if they have negative HBV DNA test.
-A history of drug and/or alcohol abuse within the past year prior to the screening visit. A history of alcohol dependence within the 5 years prior to the screening visit.
-The patient is scheduled for in-patient hospitalization including elective surgery, during the study.
-The patient has a clinically significant, uncontrolled medical condition that, in the opinion of the investigator, would put the safety of the subject 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.
-The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, has contraindications to pupillary dilation or unable to undergo magnetic resonance imaging (MRI ) [For example: patient’s weight exceeds weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc]).
-Any country-related specific regulation that would prevent the patient from entering the study.
-The patients did not adhere to treatment (<70% compliance rate) in the run-in.
-The patient has, according to World Health Organization (WHO) Grading, a cortical cataract >onequarter of the lens circumference (Grade cortical cataract-2 [COR-2]) or a posterior subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2 [PSC-2]). Patients with nuclear cataracts will not be excluded.
-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 randomization. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting GZ/SAR402671 administration.
-The patient is pregnant, or lactating.
-Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal unless the patient has the diagnosis of Gilbert syndr

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Congenital, hereditary and neonatal diseases
MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850

Intervention(s)

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Capsule
INN or Proposed INN: Venglustat
CAS Number: 1401090-53-6
Current Sponsor code: GZ/SAR402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Capsule
INN or Proposed INN: Venglustat
CAS Number: 1401090-53-6
Current Sponsor code: GZ/SAR402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1. Annualized rate of change in total kidney volume (TKV) based on magnetic resonance Imaging (MRI) from baseline to 18 months (Stage 1)
2. Annualized rate of change in estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease
Epidemiology Collaboration [CKD-EPI] equation) from baseline to 24 months (Stage 2)

Secondary Objective: -To determine the effect of venglustat on the rate of renal function decline (Stage 1) and on the rate of TKV growth (Stage 2).
-To evaluate the pharmacokinetics (PK) of venglustat in Autosomal Dominant Polycystic Kidney Disease patients (Stages 1 and 2).
- To determine the effect of venglustat on pain and fatigue, based on
patient reported diary (Stages 1 and 2).
-Safety/tolerability objective:
-To characterize the safety profile of venglustat (Stages 1 and 2).
-To evaluate the effect of venglustat on mood using Beck Depression Inventory II (BDI-II) (Stages 1 and 2).
-To evaluate the effect of venglustat on the lens by ophthalmological examination (Stages 1 and 2).
-To evaluate change in nocturia based on patient reported diary (Stages 1 and 2).
-To evaluate the effect of venglustat on kidney concentrating ability by assessing urine osmolality (in patients not on diuretic) (Stage 2 only).

Main Objective: To determine the effect of venglustat on the rate of total kidney volume (TKV) growth (Stage 1) and estimated glomerular filtration rate (eGFR) decline in patients at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Stage 2).

Timepoint(s) of evaluation of this end point: 1. From baseline to 18 months
2. From baseline to 24 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1/ 2/ :
From baseline to 18 months
3/ 4/ :
Stage 1: From baseline to 18 months Stage 2: From baseline to 24 months
5/ 6/ 7/ :
From baseline to end of treatment +30 days
8/ :
Stage 1: Day 1, Months 1, 6, and 18 Stage 2: Months 6 and 24

Secondary end point(s): 1. Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 18 months (Stage 1) : From baseline to 18 months
2. Annualized rate of change in TKV based on MRI from baseline to 18 months (Stage 2) : From baseline to 18 months
3/ Change in Brief Pain Inventory (BPI) - Item 3 from the daily symptom diary.
4/ Change in Brief Fatigue Inventory (BFI) - Item 3 from the daily symptom diary.
5. Number of adverse events (Stages 1 and 2) :
Stage 1: From baseline to 18 months
Stage 2: From baseline to 24 months
6. Change in score of BDI-II (Stages 1 & 2)
Stage 1: From baseline to 18 months
Stage 2: From baseline to 24 months
7. Change in the lens clarity from baseline by ophthalmological examination (Stages 1 and 2)
8. Assessment of single time-point plasma concentration (Stages 1 and 2)

Secondary ID(s)

EFC15392

2017-004084-12-DE

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date: 06/08/2018
Contact: