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

• Register: ClinicalTrials.gov
• Last refreshed on: 13 February 2023
• Main ID: NCT03523728
• Date of registration: 01/05/2018
• Prospective Registration: Yes
• Primary sponsor: Genzyme, a Sanofi Company
• Public title: A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients STAGED-PKD
• 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)
• Date of first enrolment: October 4, 2018
• Target sample size: 478
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03523728
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion criteria

Inclusion criteria:

- Male or female adult with ADPKD with age at the time the consent was signed:

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

2. between 18 to 50 years (both inclusive) for participants from Stage 2 with eGFR
between 45 and 89.9 milliliters per minute per 1.73 meter square (mL/min/1.73
m^2) during screening period.*

3. between 18 to 55 years (both inclusive) for participants from Stage 2 with eGFR
between 30 and 44.9 mL/min/1.73 m^2 during screening period.*

- Diagnosis of ADPKD in participants with a family history would be based on unified Pei
criteria. In the absence of a family history, the diagnosis would 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) had confirmed by a central reader prior to Visit 3.

- Estimated glomerular filtration rate between 45 to 89.9 mL/min/1.73 m^2 during
screening period* (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]
equation) for Stage 1.

- Estimated glomerular filtration rate between 30 to 89.9 mL/min/1.73 m^2 during
screening period* (CKD-EPI equation) for Stage 2.

*Eligibility would 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 participant.

- Able to read, comprehend, and respond to the study questionnaires.

- Participant had given voluntary written informed consent before performance of any
study related procedures not part of standard medical care.

- Participant had no access to tolvaptan at the time of study start or tolvaptan was not
indicated for treatment of participant according to treating physician (participant
does not meet recommended criteria for treatment, refuses to initiate or does not
tolerate treatment with tolvaptan).

- The participants, if female of childbearing potential, must have had 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 participants of childbearing potential and male participants must have had
agreed 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 greater than (>) 160 millimeters of Mercury (mmHg) 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).

- Participation in another investigational interventional study or use of IMP, within 3
months or 5 half lives, whichever was longer, before randomization.

- The participant had 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). Participants
with a positive hepatitis B surface antibody (HBsAb) test were eligible if other
criteria were met (i.e., negative tests for: HBsAg, hepatitis B core antibody
[HBcAb]). Participants immune due to natural infection (positive hepatitis B surface
antibody (HBsAb), negative hepatitis B surface antigen (HBsAg) and positive hepatitis
B core antibody [HBcAb]) were eligible if they had negative hepatitis B vaccine (HBV)
deoxyribonucleic acid (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 participant was scheduled for in-patient hospitalization including elective
surgery, during the study.

- The participant had a clinically significant, uncontrolled medical condition that, in
the opinion of the investigator, would put the safety of the participant at risk
through participation, or which would affect the efficacy or safety analysis if the
condition exacerbated during the study, or that might significantly interfere with
study compliance, including all prescribed evaluations and follow-up activities.

- The participants, in the opinion of the investigator, was unable to adhere to the
requirements of the study or unable to undergo study assessments (e.g., had
contraindications to pupillary dilation or unable to undergo magnetic resonance
imaging (MRI) [For example: participant'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 participant from
entering the study.

- The participants did not adhere to treatment (less than [<] 70 percent [%] compliance
rate) in the run-in.

- The participant had, according to World Health Organization (WHO) Grading, a cortical
cataract greater than or equal to (>=)one-quarter of the lens circumference (Grade
cortical cataract-2 [COR-2]) or a posterior subcapsular cataract >=2 millimeter (Grade
posterior subcapsular cataract-2 [PSC-2]). Participant with nuclear cataracts would
not be excluded.

- The participant was then 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 might
cause cataract, according to the Prescribing Information.

- The participant had received strong or moderate inducers or inhibitors of CYP3A4
within 14 days or 5 half-lives, whichever was longer, prior to randomization. This
also included the consumption of grapefruit, grapefruit juice, or grapefruit
containing products within 72 hours of starting venglustat administration.

- The participant was pregnant, or lactating.

- Liver enzymes (alanine aminotransferase /aspartate aminotransferase ) or total
bilirubin >2 times the upper limit of normal u


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Polycystic Kidney, Autosomal Dominant

Intervention(s)

Drug: Venglustat

Drug: Placebo

Primary Outcome(s)

Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) From Baseline to Month 24: Combined Stage 1 and Stage 2 [Time Frame: From Baseline to Month 24]

Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1 [Time Frame: From Baseline to Month 18]

Secondary Outcome(s)

Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1 [Time Frame: From Baseline to Month 18]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2 [Time Frame: From Baseline to Month 24]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2 [Time Frame: From Baseline to Month 18]

Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1 [Time Frame: From Baseline to Month 18]

Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1 [Time Frame: From Baseline to Month 24]

Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2 [Time Frame: Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24, Last on-treatment value up to last IMP + 1 day (anytime during the maximum duration of 25 months)]

Pharmacokinetics: Plasma Concentration of Venglustat: Stage 2 [Time Frame: Month 1: Pre-dose and 3 hours Post-dose]

Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2 [Time Frame: Baseline, Month 18, Month 24]

Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2 [Time Frame: From Baseline to Month 24]

Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1 [Time Frame: Day 1: 3 hours Post-Dose, Month 1: Pre-Dose and 3 hours Post-Dose, Month 6: Pre-Dose, Month 18: Pre-Dose]

Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2 [Time Frame: From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier]

Secondary ID(s)

2017-004084-12

EFC15392

U1111-1202-0775

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/11/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03523728