STAGED-PKD: A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03523728
• Collaborator: (none)
• Enrollment: 478
• Locations: 95
• Arms: 3
• Actual Duration (Months): 34
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary 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).

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).

• 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).

Condition or Disease	Intervention/Treatment	Phase
Polycystic Kidney, Autosomal Dominant	Drug: Venglustat GZ402671; Drug: Placebo	Phase 2/Phase 3

Detailed Description

Study duration per participant is 26 months (maximal) per stage, including a screening period of 15 days, run-in period of 2 weeks, a 24-month treatment period, and a follow-up 30 days after final dose of investigational medicinal product (IMP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 478 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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)
• Actual Study Start Date: Oct 4, 2018
• Actual Primary Completion Date: Aug 3, 2021
• Actual Study Completion Date: Aug 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Venglustat dose 1 Patients will receive venglustat dose 1 once daily for 24 months	Drug: Venglustat GZ402671; Pharmaceutical form: capsule Route of administration: oral
Experimental: Venglustat dose 2 Patients will receive venglustat dose 2 once daily for 24 months	Drug: Venglustat GZ402671; Pharmaceutical form: capsule Route of administration: oral
Placebo Comparator: Placebo Placebo will be given once daily (Stage 1 and Stage 2) for 24 months	Drug: Placebo; Pharmaceutical form: capsule Route of administration: oral

Outcome Measures

Primary Outcome Measures

1. Rate of change in of total kidney volume (TKV) [From baseline to 18 months]

   Annualized rate of change in total kidney volume (TKV) based on magnetic resonance imaging (MRI) from baseline to 18 months (Stage 1)

2. Rate of change in eGFR [From baseline to 24 months]

   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 Outcome Measures

1. Rate of change in eGFR [From baseline to 18 months]

   Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 18 months (Stage 1)

2. Rate of change in TKV [From baseline to 18 months]

   Annualized rate of change in TKV based on MRI from baseline to 18 months (Stage 2)

3. Change in pain [Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months]

   Change in Brief Pain Inventory (BPI) - Item 3 from the daily symptom diary

4. Change in fatigue [Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months]

   Change in Brief Fatigue Inventory (BFI) - Item 3 from the daily symptom diary

5. Number of adverse events [From baseline to end of treatment +30 days]

   Number of adverse events (Stages 1 and 2)

6. Assessment of plasma concentration of venglustat [Stage 1: Day 1, Months 1, 6, and 18; Stage 2: Months 6 and 24]

   Assessment of single time-point plasma concentration (Stages 1 and 2)

7. Change in lens clarity [From baseline to end of treatment +30 days]

   Change in the lens clarity from baseline by ophthalmological examination (Stages 1 and 2)

8. Change in score of Beck Depression Inventory-II (BDI-II) [From baseline to end of treatment +30 days]

   Change in score of BDI-II (Stages 1 and 2)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male or female adult with Autosomal Dominant Polycystic Kidney Disease (ADPKD) with age at the time the consent is signed:

1. between 18 to 50 years (both inclusive) for patients from Stage 1

2. 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*

3. 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 AKPKD 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**

**Total kidney volume (TKV) 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 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 (β-human chorionic gonadotropin [β-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.

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 antigen (HBsAb), negative hepatitis B surface antibody (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 >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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8400002	Birmingham	Alabama	United States	35294
2	Investigational Site Number 8400017	Los Angeles	California	United States	90024
3	Investigational Site Number 8400001	San Francisco	California	United States	94143
4	Investigational Site Number 8400008	Aurora	Colorado	United States	80045
5	Investigational Site Number 8400010	New Haven	Connecticut	United States	06510
6	Investigational Site Number 8400004	Atlanta	Georgia	United States	30322
7	Investigational Site Number 8400007	Chicago	Illinois	United States	60637
8	Investigational Site Number 8400014	Iowa City	Iowa	United States	52242
9	Investigational Site Number 8400003	Kansas City	Kansas	United States	66103
10	Investigational Site Number 8400021	Baltimore	Maryland	United States	21201
11	Investigational Site Number 8400016	Boston	Massachusetts	United States	02111
12	Investigational Site Number 8400020	Rochester	Minnesota	United States	55905
13	Investigational Site Number 8400027	Kansas City	Missouri	United States	64111
14	Investigational Site Number 8400011	Philadelphia	Pennsylvania	United States	19104
15	Investigational Site Number 8400015	San Antonio	Texas	United States	78215
16	Investigational Site Number 8400019	Morgantown	West Virginia	United States	26506
17	Investigational Site Number 8400005	Madison	Wisconsin	United States	53792
18	Investigational Site Number 8400006	Milwaukee	Wisconsin	United States	53226
19	Investigational Site Number 0320001	Buenos Aires		Argentina	C1429BWN
20	Investigational Site Number 0320003	Santa Fe		Argentina	S3000EPV
21	Investigational Site Number 0360002	Herston		Australia	4029
22	Investigational Site Number 0360003	Nedlands		Australia	6009
23	Investigational Site Number 0360001	Westmead		Australia	2145
24	Investigational Site Number 0400001	Graz		Austria	8036
25	Investigational Site Number 0400004	Wien		Austria	1090
26	Investigational Site Number 0560001	Bruxelles		Belgium	1200
27	Investigational Site Number 0560002	Leuven		Belgium	3000
28	Investigational Site Number 1240002	Edmonton		Canada	T6G 2B7
29	Investigational Site Number 1240003	Montreal		Canada	H2W 1R7
30	Investigational Site Number 1240001	Toronto		Canada	M5G 2N2
31	Investigational Site Number 1560005	Beijing		China	100853
32	Investigational Site Number 1560004	Chengdu		China	610041
33	Investigational Site Number 1560009	Guangzhou		China	510080
34	Investigational Site Number 1560006	Hangzhou		China	310003
35	Investigational Site Number 1560002	Hefei		China	230022
36	Investigational Site Number 1560007	Nanjing		China	210009
37	Investigational Site Number 1560008	Nanjing		China	210029
38	Investigational Site Number 1560001	Shanghai		China	200003
39	Investigational Site Number 1560003	Shenyang		China	110004
40	Investigational Site Number 2030001	Praha 2		Czechia	12808
41	Investigational Site Number 2030002	Praha 4		Czechia	14021
42	Investigational Site Number 2080001	Copenhagen		Denmark	2100
43	Investigational Site Number 2080002	Roskilde		Denmark	4000
44	Investigational Site Number 2500004	Bordeaux		France	33076
45	Investigational Site Number 2500003	Brest		France	29609
46	Investigational Site Number 2500002	Paris		France	75015
47	Investigational Site Number 2500001	Toulouse		France	31403
48	Investigational Site Number 2760001	Berlin		Germany	10117
49	Investigational Site Number 2760002	Dresden		Germany	01307
50	Investigational Site Number 2760010	Dresden		Germany	01307
51	Investigational Site Number 2760007	Düsseldorf		Germany	40210
52	Investigational Site Number 2760009	Essen		Germany	45122
53	Investigational Site Number 2760005	Hannover		Germany	30625
54	Investigational Site Number 2760003	Köln		Germany	50937
55	Investigational Site Number 2760011	Leipzig		Germany	04103
56	Investigational Site Number 2760012	Mainz		Germany	55131
57	Investigational Site Number 2760004	München		Germany	81675
58	Investigational Site Number 3760003	Ashdod		Israel	7747629
59	Investigational Site Number 3760002	Reẖovot		Israel	76100
60	Investigational Site Number 3800001	Brescia		Italy	25123
61	Investigational Site Number 3800002	Milano		Italy	20132
62	Investigational Site Number 3800003	Napoli		Italy	80131
63	Investigational Site Number 3920002	Bunkyo-Ku		Japan
64	Investigational Site Number 3920005	Kamakura-Shi		Japan
65	Investigational Site Number 3920006	Kawasaki-Shi		Japan
66	Investigational Site Number 3920010	Kyoto-Shi		Japan
67	Investigational Site Number 3920009	Nagoya-Shi		Japan
68	Investigational Site Number 3920003	Niigata-Shi		Japan
69	Investigational Site Number 3920007	Osaka-Shi		Japan
70	Investigational Site Number 3920001	Sapporo-Shi		Japan
71	Investigational Site Number 3920004	Shinjuku-Ku		Japan
72	Investigational Site Number 3920008	Toyoake-Shi		Japan
73	Investigational Site Number 4100001	Seoul		Korea, Republic of	03080
74	Investigational Site Number 4100002	Seoul		Korea, Republic of	07061
75	Investigational Site Number 5280003	Amsterdam		Netherlands	1105AZ
76	Investigational Site Number 5280001	Groningen		Netherlands	9713 GZ
77	Investigational Site Number 5280002	Nijmegen		Netherlands	6525 GA
78	Investigational Site Number 6160003	Warszawa		Poland	04-141
79	Investigational Site Number 6160002	Wrocław		Poland	50-556
80	Investigational Site Number 6160001	Łódź		Poland	92-213
81	Investigational Site Number 6200004	Almada		Portugal	2801-951
82	Investigational Site Number 6200005	Carnaxide		Portugal	2790-134
83	Investigational Site Number 6200001	Loures		Portugal	2674-514
84	Investigational Site Number 6420002	Bucuresti		Romania	022328
85	Investigational Site Number 6420004	Oradea		Romania	410469
86	Investigational Site Number 6420001	Timisoara		Romania	300723
87	Investigational Site Number 7240003	Barcelona		Spain	08003
88	Investigational Site Number 7240001	Barcelona		Spain	08025
89	Investigational Site Number 7240002	Madrid / Madrid		Spain	28040
90	Investigational Site Number 1580001	Taichung		Taiwan	40447
91	Investigational Site Number 1580002	Taipei		Taiwan	10043
92	Investigational Site Number 7920001	Istanbul		Turkey
93	Investigational Site Number 7920002	Kayseri		Turkey	38039
94	Investigational Site Number 7920003	Kocaeli		Turkey	41380
95	Investigational Site Number 8260001	Sheffield		United Kingdom	S5 7AU

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• For more information in Japan, please click here
• For more information in Germany/Austria, please click here

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03523728
• Other Study ID Numbers: EFC15392; 2017-004084-12; U1111-1202-0775
• First Posted: May 14, 2018
• Last Update Posted: Apr 25, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant

Study Results

No Results Posted as of Apr 25, 2022