Fabry Disease
Conditions
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 an additional 12 months or until the Common Study End of Treatment Day (CSEOTD).
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)
Interventions
Pharmaceutical form: Tablet Route of administration: Oral
DRUGPlacebo
Pharmaceutical form: Tablet Route of administration: Oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants enrolled in the open-label extension will be treated with venglustat only.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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, or abdominal pain) | From baseline to 6 months |
| 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, or abdominal pain) | From baseline to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 | — |
| 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 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Italy, Japan, Mexico, Norway, Poland, Romania, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed