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

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ClinicalTrials.gov Identifier: NCT03523728
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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).

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 560 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 : October 4, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

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




Primary Outcome Measures :
  1. Rate of change in of total kidney volume (TKV) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From baseline to 18 months ]
    Annualized rate of change in TKV based on MRI from baseline to 18 months (Stage 2)

  3. Change in urine osmolality [ Time Frame: From baseline to 24 months ]
    Change in urine osmolality from baseline to 24 months (in patients not on diuretic) (Stage 2)

  4. Change in nocturia [ Time Frame: Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months ]
    Change in nocturia from baseline to 18 months (Stage 1) and from baseline to 24 months (Stage 2)

  5. Adverse events [ Time Frame: Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months ]
    Number of adverse events (Stages 1 and 2)

  6. Assessment of plasma concentration of venglustat [ Time Frame: 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 [ Time Frame: Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months ]
    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) [ Time Frame: Stage 1: From baseline to 18 months; Stage 2: From baseline to 24 months ]
    Change in score of BDI-II (Stages 1 and 2)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03523728


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

Locations
United States, Texas
Investigational Site Number 8400015 Recruiting
San Antonio, Texas, United States, 78215
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03523728     History of Changes
Other Study ID Numbers: EFC15392
2017‐004084‐12 ( EudraCT Number )
U1111-1202-0775 ( Other Identifier: UTN )
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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://www.clinicalstudydatarequest.com/

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
Kidney Diseases, Cystic
Kidney Diseases
Urologic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn