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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03523728




Registration number
NCT03523728
Ethics application status
Date submitted
1/05/2018
Date registered
14/05/2018
Date last updated
13/08/2019

Titles & IDs
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)
Secondary ID [1] 0 0
2017-004084-12
Secondary ID [2] 0 0
EFC15392
Universal Trial Number (UTN)
Trial acronym
STAGED-PKD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycystic Kidney, Autosomal Dominant 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venglustat GZ402671
Treatment: Drugs - Placebo

Experimental: Venglustat dose 1 - Patients will receive venglustat dose 1 once daily for 24 months

Experimental: Venglustat dose 2 - Patients will receive venglustat dose 2 once daily for 24 months

Placebo Comparator: Placebo - Placebo will be given once daily (Stage 1 and Stage 2) for 24 months


Treatment: Drugs: Venglustat GZ402671
Pharmaceutical form: capsule Route of administration: oral

Treatment: Drugs: Placebo
Pharmaceutical form: capsule Route of administration: oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of change in of total kidney volume (TKV) - Annualized rate of change in total kidney volume (TKV) based on magnetic resonance imaging (MRI) from baseline to 18 months (Stage 1)
Timepoint [1] 0 0
From baseline to 18 months
Primary outcome [2] 0 0
Rate of change in eGFR - 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)
Timepoint [2] 0 0
From baseline to 24 months
Secondary outcome [1] 0 0
Rate of change in eGFR - Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 18 months (Stage 1)
Timepoint [1] 0 0
From baseline to 18 months
Secondary outcome [2] 0 0
Rate of change in TKV - Annualized rate of change in TKV based on MRI from baseline to 18 months (Stage 2)
Timepoint [2] 0 0
From baseline to 18 months
Secondary outcome [3] 0 0
Change in urine osmolality - Change in urine osmolality from baseline to 24 months (in patients not on diuretic) (Stage 2)
Timepoint [3] 0 0
From baseline to 24 months
Secondary outcome [4] 0 0
Change in nocturia - Change in nocturia from baseline to 18 months (Stage 1) and from baseline to 24 months (Stage 2)
Timepoint [4] 0 0
Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months
Secondary outcome [5] 0 0
Adverse events - Number of adverse events (Stages 1 and 2)
Timepoint [5] 0 0
Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months
Secondary outcome [6] 0 0
Assessment of plasma concentration of venglustat - Assessment of single time-point plasma concentration (Stages 1 and 2)
Timepoint [6] 0 0
Stage 1: Day 1, Months 1, 6, and 18; Stage 2: Months 6 and 24
Secondary outcome [7] 0 0
Change in lens clarity - Change in the lens clarity from baseline by ophthalmological examination (Stages 1 and 2)
Timepoint [7] 0 0
Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months
Secondary outcome [8] 0 0
Change in score of Beck Depression Inventory-II (BDI-II) - Change in score of BDI-II (Stages 1 and 2)
Timepoint [8] 0 0
Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months

Eligibility
Key inclusion criteria
Inclusion criteria:

- Male or female adult with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
diagnosed by unified Pei criteria between ages of 18 to 50 years (both inclusive) at
screening.

- Mayo Imaging Classification of ADPKD Class 1C, 1D or 1E (3).

- Estimated glomerular filtration rate between 45 to 90 mL/min/1.73 m2 at screening
(Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]).

- Stable treatment regimen of antihypertensive therapy for at least 30 days prior to the
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 (ß-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.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 documented diagnosis of any of the following infections: hepatitis
B, hepatitis C, human immunodeficiency virus 1 or 2. Patients with a positive
hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B
immunization are eligible if other criteria are met (ie, negative tests for: HBsAg,
hepatitis B core antibody [HBcAb]).Patients with positive hepatitis B core antibody
[HBcAb], negative HBsAg and negative hepatitis B surface antibody (HBsAb) tests are
eligible if they have HBV DNA negative test.

- A history of drug and/or alcohol abuse within the past year 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 >one-quarter 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 venglustat 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 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 3mg/dl (51 µmol/L) with conjugated bilirubin less than
20% of the total bilirubin fraction.

- Presence of severe depression as measured by Beck Depression Inventory-II (BDI-II) >28
and/or a history of a major affective disorder within 1 year of the screening visit.

- Known hypersensitivity to venglustat or any component of the excipients.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360002 - Herston
Recruitment hospital [2] 0 0
Investigational Site Number 0360001 - Westmead
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
West Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Canada
State/province [18] 0 0
Edmonton
Country [19] 0 0
Canada
State/province [19] 0 0
Montreal
Country [20] 0 0
Canada
State/province [20] 0 0
Toronto
Country [21] 0 0
China
State/province [21] 0 0
Chengdu
Country [22] 0 0
China
State/province [22] 0 0
Hefei
Country [23] 0 0
China
State/province [23] 0 0
Shanghai
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha 2
Country [25] 0 0
Czechia
State/province [25] 0 0
Praha 4
Country [26] 0 0
Denmark
State/province [26] 0 0
København Ø
Country [27] 0 0
Denmark
State/province [27] 0 0
Roskilde
Country [28] 0 0
France
State/province [28] 0 0
Brest
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Toulouse
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Dresden
Country [33] 0 0
Germany
State/province [33] 0 0
Düsseldorf
Country [34] 0 0
Germany
State/province [34] 0 0
Hannover
Country [35] 0 0
Germany
State/province [35] 0 0
Köln
Country [36] 0 0
Germany
State/province [36] 0 0
München
Country [37] 0 0
Italy
State/province [37] 0 0
Milano
Country [38] 0 0
Italy
State/province [38] 0 0
Montichiari
Country [39] 0 0
Japan
State/province [39] 0 0
Bunkyo-Ku
Country [40] 0 0
Japan
State/province [40] 0 0
Kamakura-Shi
Country [41] 0 0
Japan
State/province [41] 0 0
Kawasaki-Shi
Country [42] 0 0
Japan
State/province [42] 0 0
Kyoto-Shi
Country [43] 0 0
Japan
State/province [43] 0 0
Nagoya-Shi
Country [44] 0 0
Japan
State/province [44] 0 0
Niigata-Shi
Country [45] 0 0
Japan
State/province [45] 0 0
Osaka-Shi
Country [46] 0 0
Japan
State/province [46] 0 0
Sapporo-Shi
Country [47] 0 0
Japan
State/province [47] 0 0
Shinjuku-Ku
Country [48] 0 0
Japan
State/province [48] 0 0
Toyoake-Shi
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Seoul
Country [50] 0 0
Netherlands
State/province [50] 0 0
Groningen
Country [51] 0 0
Netherlands
State/province [51] 0 0
Nijmegen
Country [52] 0 0
Portugal
State/province [52] 0 0
Almada
Country [53] 0 0
Portugal
State/province [53] 0 0
Loures
Country [54] 0 0
Romania
State/province [54] 0 0
Bucuresti
Country [55] 0 0
Romania
State/province [55] 0 0
Timisoara
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

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

Secondary Objectives:

- 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).

- 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).
Trial website
https://clinicaltrials.gov/show/NCT03523728
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03523728