Clinical trial NCT05280548: A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease
Official title: A Randomized, Open-label, Parallel-group, 18-month Phase 3 Study to Evaluate the Effect of Venglustat Compared With Usual Standard of Care on Left Ventricular Mass Index in Participants With Fabry Disease and Left Ventricular Hypertrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Fabry Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-03-15
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an 18-month, multicenter, randomized, active-control, parallel-group Phase 3 study, in which participants will be randomized to venglustat versus standard of care therapy (agalsidase alfa, agalsidase beta, or migalastat) to evaluate the effect of venglustat on left ventricular mass index (LVMI) in adult participants with Fabry disease and left ventricular hypertrophy.

* Study visits will take place approximately every 3 to 6 months
* Participants who complete the randomized period may continue to the long-term extension (LTE) to receive venglustat for up to additional 45 months with the total study duration up to 5.3 years maximum.

Detailed description: Randomized period: the total duration will be up to approximately of 20 months (1 month screening 18 months of treatment and a possible follow-up period of 1 month if no participation in the long-term extension period)

Long-term extension period: the total duration will be from minimum 19 months (18 months of treatment and 1 month of follow-up period) to maximum 46 months (45 months of treatment and 1 month of follow-up period). The maximum total study duration is approximately 5.3 years

Eligibility criteria: Inclusion Criteria:

* Male and female participants aged 18 to 65 with previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease.
* Participants may be receiving treatment with agalsidase alfa, agalsidase beta, or migalastat, or may be untreated.
* Left ventricular hypertrophy.
* Contraception for male or female participants: not pregnant or breastfeeding; no sperm donating for male participant.
* A signed informed consent must be provided prior to any study-related procedures.

Exclusion Criteria:

* History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery or kidney transplantation.
* History of seizures currently requiring treatment.
* Underlying medical condition that may cause or contribute to left ventricular hypertrophy.
* Asymmetric hypertrophy by cardiac MRI at screening if considered by central reader to be not related to Fabry disease.
* Advanced cardiac fibrosis, defined as significant late gadolinium enhancement affecting 3 or more segments involving \>50% of myocardial thickness on screening cardiac MRI.
* History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.
* Estimated glomerular filtration rate \<45 mL/min/1.73m2.
* Presence of severe depression as measured by Beck's Depression Inventory (BDI)-II \>28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.
* Patients with hepatitis C, HIV, or hepatitis B infection.
* Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID-19 requiring hospitalization within 6 months of enrollment.
* History of drug and/or alcohol abuse.
* Moderate to severe hepatic impairment.
* History of or active hepatobiliary disease.
* Liver enzymes (alanine aminotransferase/aspartate aminotransferase) or total bilirubin \>2 times the upper limit of normal.
* Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to randomization.
* Known contraindication to undergoing MRI or known hypersensitivity to gadolinium-based contrast agents.

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

Primary outcomes:
measure: Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)
timeFrame: from baseline to 18 months
Secondary outcomes:
measure: Slope of estimated glomerular filtration rate (eGFR) as assessed by the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation
timeFrame: from baseline to 18 months
measure: Change in T1 relaxation time, measured by cardiac MRI (central reading)
timeFrame: from baseline to 18 months
measure: Change in global longitudinal strain, measured by echocardiography (central reading)
timeFrame: from baseline to 18 months
measure: Percent Change in tiredness component of FD-PRO
timeFrame: from baseline to 18 months
measure: Percent Change in swelling in lower extremities component of FD-PRO
timeFrame: from baseline to 18 months
measure: Number of participants with adverse event (AE) and serious adverse event (SAE)
timeFrame: from baseline to 18 months
measure: Change in Beck Depression Inventory-II (BDI-II) score
timeFrame: from baseline to 18 months
measure: Change in the lens clarity by ophthalmological examination
timeFrame: from baseline to 18 months
measure: Plasma venglustat concentrations at prespecified visits over the study duration
timeFrame: from baseline to 18 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama -The Kirklin Clinic- Site Number : 8400010
state: Alabama
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center- Site Number : 8400008
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine - Atlanta- Site Number : 8400009
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago- Site Number : 8400005
state: Illinois
city: Hawthorne
country: United States
facility: Maryam Banikazemi, MD- Site Number : 8400001
state: New York
city: Dallas
country: United States
facility: Renal Disease Research Institute- Site Number : 8400012
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Hospital- Site Number : 8400006
state: Utah
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center (LDRTC)- Site Number : 8400004
state: Virginia
city: Graz
country: Austria
facility: Investigational Site Number : 0400001
city: Calgary
country: Canada
facility: Investigational Site Number : 1240003
state: Alberta
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240006
state: Alberta
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240002
state: British Columbia
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Beijing
country: China
facility: Investigational Site Number : 1560002
city: Beijing
country: China
facility: Investigational Site Number : 1560005
city: Chengdu
country: China
facility: Investigational Site Number : 1560001
city: Guangzhou
country: China
facility: Investigational Site Number : 1560007
city: Shanghai
country: China
facility: Investigational Site Number : 1560003
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Garches
country: France
facility: Investigational Site Number : 2500001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760003
city: Hochheim Am Main
country: Germany
facility: Investigational Site Number : 2760004
city: Mainz
country: Germany
facility: Investigational Site Number : 2760005
city: Würzburg
country: Germany
facility: Investigational Site Number : 2760001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Athens
country: Greece
facility: Investigational Site Number : 3000003
city: Heraklion
country: Greece
facility: Investigational Site Number : 3000001
city: Milan
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Naples
country: Italy
facility: Investigational Site Number : 3800002
state: Napoli
city: Naples
country: Italy
facility: Investigational Site Number : 3800003
state: Napoli
city: Bologna
country: Italy
facility: Investigational Site Number : 3800004
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920006
state: Hokkaido
city: Kagoshima-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Kagoshima
city: Kagoshima-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Kagoshima
city: Kawasaki
country: Japan
facility: Investigational Site Number : 3920005
state: Kanagawa
city: Sendai
country: Japan
facility: Investigational Site Number : 3920002
state: Miyagi
city: Fukuoka
country: Japan
facility: Investigational Site Number : 3920004
city: Tokyo
country: Japan
facility: Investigational Site Number : 3920001
city: Yangsan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Bergen
country: Norway
facility: Investigational Site Number : 5780001
city: Lodz
country: Poland
facility: Investigational Site Number : 6160003
state: Lódzkie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160001
city: Madrid
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid, Comunidad De
city: Alicante
country: Spain
facility: Investigational Site Number : 7240003
city: Pontevedra
country: Spain
facility: Investigational Site Number : 7240001
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Izmit
country: Turkey
facility: Investigational Site Number : 7920003
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations Clinical Sciences and Operations
role: STUDY_DIRECTOR
References: