A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease
- Conditions
- Fabry Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT05206773
- Lead Sponsor
- Sanofi
- Brief Summary
This is a 12-month, parallel treatment, Phase 3, double-blind, randomized, placebo controlled study to evaluate the effect of venglustat on neuropathic and abdominal pain symptoms of Fabry disease in participants ≥16 years of age with Fabry disease who are treatment-naïve or untreated for at least 6 months.
* Study visits will take place approximately every 3 months.
* The double-blind period will be followed by an open-label extension (OLE) during which participants who have completed the double-blind period will be treated with venglustat for up to an additional 12 months.
- Detailed Description
Double blind period: the total duration will be up to approximately of 14 months (1 month of screening 12 month of treatment period, and a possible follow-up period of 1 month if no participation in the open label extension period)
Open-label extension period: the total duration will be approximately of 46 months (12 month of OLE treatment, additional OLE treatment until a common study end of treatment date (CSEOTD, approximately 33 months), and 1 month of follow-up period)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 122
- Male and female adult patients 16 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
- Patients who are treatment-naïve or without prior treatment with an approved or experimental therapy for Fabry disease within at least 6 months prior to screening.
- Average score of ≥3 (0=no symptom, 10=symptom as bad as you can imagine) on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD-PRO) at screening.
- Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
- Weight ≥30 Kg
- A signed informed consent must be provided prior to any study-related procedures.
- Any manifestations of Fabry disease that preclude placebo administration.
- History of transient ischemic attack, stroke, myocardial infarction, heart failure, evidence of left ventricular hypertrophy and/or cardiac fibrosis, major cardiovascular surgery, or kidney transplantation.
- 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.
- Patients with hepatitis C, HIV, or hepatitis B infection.
- Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
- History of seizures currently requiring treatment.
- Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP >=150 or diastolic BP >=100 at screening.
- Estimated glomerular filtration rate <60 mL/min/1.73m².
- Urine protein to creatinine ratio >= 1 g/g at screening.
- 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.
- Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
- Moderate to severe hepatic impairment.
- History of drug and/or alcohol abuse.
- History of or active hepatobiliary disease.
- Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin >2 times the upper limit of normal (ULN).
- Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
- Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half-lives, whichever is longer, prior to randomization.
The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Venglustat Venglustat (GZ402671) Participant will receive venglustat dose once daily up to 12 months Placebo Placebo Participants will receive placebo once daily up to 12 months
- Primary Outcome Measures
Name Time Method Percent change from baseline at 12 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, and abdominal pain) From baseline to 12 months Percent change from baseline at 6 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, and abdominal pain) From baseline to 6 months
- Secondary Outcome Measures
Name Time Method Percent change in tiredness component of FD-PRO From baseline to 6 month and 12 months Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO At 6 months and 12 months Response is defined as at least a 30% decrease from baseline in the most bothersome of 3 FD-PRO items between neuropathic pain in upper extremities, neuropathic pain in lower extremities, and abdominal pain
Number of participants with adverse event (AE) and serious adverse event (SAE) From baseline to 6 month and 12 months Percent change in plasma globotriaosylsphingosine (lyso-GL-3) From baseline to 6 month and 12 months Frequency of rescue pain medication use From baseline to 6 months and 12 months Number of days with use of rescue pain medications during the 6-month treatment period, divided by duration of the 6-month treatment period and multiplied by 100. The same definition will be used for the 12-month period.
Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7) From baseline to 6 month and 12 months Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6) From baseline to 12 months Change in Beck Depression Inventory-II (BDI-II) score From baseline to 6 month and 12 months Plasma venglustat concentrations at prespecified visits over the study duration From baseline to 6 month and 12 months Maximum venglustat plasma concentration (Cmax) From baseline to 6 month and 12 months Time to maximum venglustat plasma concentration (tmax) From baseline to 6 month and 12 months Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24) From baseline to 6 month and 12 months
Trial Locations
- Locations (58)
Nephrology Clinic at Kirklin Clinic of UAB Hospital_Investigational Site Number: 8400011
🇺🇸Birmingham, Alabama, United States
UCLA Medical Center_Investigational Site Number: 8400006
🇺🇸Los Angeles, California, United States
University of California Irvine Medical Center- Site Number : 8400019
🇺🇸Orange, California, United States
Advent Health Orlando_Investigational Site Number: 8400008
🇺🇸Orlando, Florida, United States
Emory Genetics- Site Number : 8400010
🇺🇸Atlanta, Georgia, United States
Westchester Medical Center Healthcare Corporation- Site Number : 8400001
🇺🇸Hawthorne, New York, United States
Cincinnati Children's Hospital Medical Center - PIN- Site Number : 8400013
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Site Number : 8400016
🇺🇸Cleveland, Ohio, United States
Children's Hospital Of Pittsburgh- Site Number : 8400009
🇺🇸Pittsburgh, Pennsylvania, United States
Renal Disease Research Institute, An affiliate of: Dallas Nephrology Associates_Investigational Site Number: 8400012
🇺🇸Dallas, Texas, United States
University Of Utah Health Sciences Center- Site Number : 8400005
🇺🇸Salt Lake City, Utah, United States
Lysosomal and Rare Disorders Research and Treatment Center_Investigational Site Number: 8400004
🇺🇸Fairfax, Virginia, United States
Fundacion Cori para la Investigación y Prevención del Cancer_Investigational Site Number: 0320002
🇦🇷La Rioja, Argentina
Instituto de Investigaciones Clínicas Quilmes (IICQ) SRL_Investigational Site Number: 0320003
🇦🇷Quilmes, Argentina
Investigational Site Number : 0360001
🇦🇺Parkville, Victoria, Australia
Investigational Site Number: 0400001
🇦🇹Vienna, Austria
Hospital de Clínicas de Porto Alegre_Investigational Site Number: 0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto de Genética e Erros Inatos do Metabolismo - IGEIM- Site Number : 0760002
🇧🇷São Paulo, Brazil
M.A.G.I.C Calgary LTD_Investigational Site Number: 1240003
🇨🇦Calgary, Alberta, Canada
Medicine Dalhousie University_Investigational Site Number : 1240001
🇨🇦Halifax, Nova Scotia, Canada
University Health Network_Investigational Site Number : 1240005
🇨🇦Toronto, Ontario, Canada
No.8, Xishiku Street, Xicheng District_Site Number: 1560001
🇨🇳Beijing, China
No.197,2nd Ruijin road, Huangpu district_Site Number: 1560003
🇨🇳Shanghai, China
No.85 South Jiefang road, Yingze District_Site Number: 1560004
🇨🇳Taiyuan, China
Investigational Site Number : 1560006
🇨🇳Zhengzhou, China
Investigational Site Number: 2460001
🇫🇮Turku, Finland
Investigational Site Number : 2500001
🇫🇷Garches, France
Investigational Site Number: 2080001
🇩🇰Copenhagen, Denmark
ISphinCS GmbH_Investigational Site Number: 2760004
🇩🇪Hochheim Am Main, Germany
Investigational Site Number: 2760001
🇩🇪Wurzburg, Germany
Investigational Site Number : 3000003
🇬🇷Athens, Greece
IRCCS Policlinico di Sant'Orsola_Investigational Site Number : 3800005
🇮🇹Bologna, Italy
Azienda Ospedaliera Universitaria "Federico II", U.O. di Nefrologia- Diparimento di Sanità Pubblica_Investigational Site Number: 3800001
🇮🇹Napoli, Italy
Azienda Ospedaliera Universitaria_Investigational Site Number: 3800003
🇮🇹Palermo, Italy
Fukuoka University Hospital_Investigational Site Number: 3920004
🇯🇵Fukuoka-shi, Fukuoka, Japan
The Jikei University Hospital_Investigational Site Number: 3920003
🇯🇵Minato-ku, Tokyo, Japan
Tohoku University Hospital_Investigational Site Number: 3920001
🇯🇵Sendai-shi, Miyagi, Japan
Investigational Site Number : 2760005
🇩🇪Mainz, Germany
Investigational Site Number: 2760003
🇩🇪München, Germany
University Hospital of Heraklion_Investigational Site Number: 3000001
🇬🇷Heraklion, Greece
University Hospital of Ioannina_Investigational Site Number: 3000002
🇬🇷Ioannina, Greece
Fondazione IRCCS San Gerardo dei Tintori, S.C. Nefrologia - Clinica Nefrologica_Investigational Site Number: 3800002
🇮🇹Monza, Italy
Fondazione Policlinico Universitario_Investigational Site Number: 3800004
🇮🇹Roma, Italy
Investigational Site Number : 3920005
🇯🇵Kawasaki, Kanagawa, Japan
Hospital Universitario "Dr. José Eleuterio González" Departamento de Genética Centro Universitario contra el cáncer_Investigational Site Number: 4840001
🇲🇽Monterrey, Nuevo León, Mexico
Odette del Carmen DIAZ-AVENDAÑO Clinstile, S.A. de C.V. Durango_Investigational Site Number: 4840002
🇲🇽Ciudad de Mexico, Mexico
Investigational Site Number: 5780001
🇳🇴Bergen, Norway
Investigational Site Number : 6160002
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 6160004
🇵🇱Rzeszow, Poland
Investigational Site Number: 6160003
🇵🇱Wroclaw, Poland
Institutul Clinic Fundeni_Investigational Site Number: 6420001
🇷🇴Bucuresti, Romania
Investigational Site Number : 7560001
🇨🇭Zürich, Switzerland
Investigational Site Number : 7920001
🇹🇷Ankara, Turkey
Investigational Site Number : 7920002
🇹🇷Izmit, Turkey
Investigational Site Number : 7920004
🇹🇷Malatya, Turkey
Investigational Site Number: 8260001
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Investigational Site Number: 8260002
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 8260003
🇬🇧Salford, Manchester, United Kingdom