MedDRA version: 24.1 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
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 = 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 CYP3A within 14 days or 5 half lives, whichever is longer, prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of venglustat on neuropathic or abdominal pain in participants =16 Years of Age with Fabry disease patients who are treatment-naïve or untreated for at least 6 months prior to screening;Secondary Objective: - To assess the effect of venglustat on plasma globotriaosylsphingosine (lyso-GL-3) levels - To assess the effect of venglustat on the rescue pain medication use - To evaluate the effect of venglustat on symptoms of Fabry disease - To assess the safety and tolerability of venglustat in patients with Fabry disease - To evaluate the pharmacokinetics (PK) of venglustat in patients with Fabry disease;Primary end point(s): 1/ 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) 2/ 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);Timepoint(s) of evaluation of this end point: 1/ From baseline to 6 months 2/ From baseline to 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Percent change in plasma globotriaosylsphingosine (lyso-GL-3) 2 - Frequency of rescue pain medication use: 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. 3 - Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7) 4- Percent change in tiredness component of FD-PRO 5 - Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO: 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. 6 - Number of participants with adverse event (AE) and serious adverse event (SAE) 7 Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6) 8 Change in Beck Depression Inventory-II (BDI-II) score 9 - Plasma venglustat concentrations at prespecified visits over the study duration 10 - Maximum venglustat plasma concentration (Cmax) 11 - Time to maximum venglustat plasma concentration (tmax) 12 - Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24);Timepoint(s) of evaluation of this end point: For 1 to 4, 6 and for 8 to 12: From baseline to 6 month and 12 months 5: At 6 months and 12 months 7: From baseline to 12 months | — |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, China, Denmark, Finland, France, Germany, Greece, Italy, Mexico, Netherlands, Norway, Poland, Romania, Russian Federation, Switzerland, Türkiye, Ukraine, United Kingdom
Contacts
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Sanofi Aventis AEBE
Outcome results
None listed