Fabry disease MedDRA version: 17.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: GZ402671 / SAR402671
Pharmaceutical Form: Capsule
CAS Number: 1401090-53-6
Current Sponsor code: SAR402671 / GZ402671
Other descriptive name: Genz-682452-AA
Concentration unit: mg millig
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: The patient is =18 years of age and 80 ng/mL. The patient has never been treated with a Fabry disease-specific treatment. If the patient is on renin-angiotensin-aldosterone system (RAAS) blockers and antidepressants, the dose should be stable (ie, prescribed dose and frequency) for at least the immediate 3 months prior to screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The patient has an estimated glomerular filtration rate (eGFR) the upper limit of normal, or serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] >2.0 times the upper limit of normal). The patient has, according to World Health Organization (WHO) Grading a cortical cataract (COR) >one-quarter of the lens circumference (Grade COR-2) or a posterior subcapsular cataract (PSC) >2 mm (Grade PSC-2). Patients with nuclear cataracts are not excluded. The patient is being administered a chronic regimen (more frequently than every 2 weeks) of any dose or route of corticosteroids or any medication that may cause cataract, according to the prescribing information. The patient has received strong or moderate inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) per Food and Drug Administration (FDA) classification within 14 days prior to enrolment or within 5 times the elimination half-life or PD half-life of the medication, whichever is longer. The patient is scheduled for in-patient hospitalization, including elective surgery, during the study. The patient has a positive result on 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). Patients with a positive hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B immunization are eligible if other criteria are met (ie, negative tests for: HBsAg, hepatitis B core antibody [HBcAb], and hepatitis C virus antibody [HCVAb]). The patient has participated in a study involving an investigational drug within the past 30 days of the start of the trial. The patient is unwilling to comply with the requirements of the protocol. The patient is a sexually active man who is not willing to use 2 forms of birth control including a barrier method during the study. The patient has history or ongoing clinically significant cardiac arrhythmia, defined as either atrial fibrillation, sustained or non-sustained ventricular tachycardia The patient has any contraindication to magnetic resonance imaging (MRI). The patient has one of the following central nervous system exclusion criteria: Acute stroke, within 3 months of the screening visit. History of seizures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and exploratory efficacy of GZ402671 / SAR402671 in enzyme replacement therapy treatment-naïve adult male patients diagnosed with Fabry disease.;Secondary Objective: Not applicable;Primary end point(s): Change from baseline in globotriaosylceramide (GL-3) scores as evaluated by light microscopy (LM) in superficial skin capillary;Timepoint(s) of evaluation of this end point: 26 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 30 weeks 1)Change from baseline in GL-3, lyso GL-3, and plasma glucosylceramide (GL-1) 2)Change from baselline in scores of GL-3 from other cell types in skin biopsy using LM 3)Urine GL-3 change from baseline Up to 54 weeks 4) Characterization of the safety profile of GZ402671, including the frequency, duration, and severity of adverse events (AEs) 26 weeks 5) Assessment PK parameters – peak concetration (Cmax), Dose-Corrected Observed Plasma Trough Concentrations (Ctrough),and time to reach max concentration (tmax) 6) Assessment of PK parameters - terminal half-life (t1/2z), area under the concentration-time curve from 0 to 24 hours (AUC0-24), and plasma clearance at steady state (CLss/F) 7) Assessment of PK parameters - volume of distribution at steady-state (Vss/F) and cumulated amount excreted in urine from 0 to 24 hours (Ae0-24) 8) Assessment of PK parameters- fraction of dose excreted in urine from 0 to 24 hours (Fe0-24) and renal clearance of the drug determined in 0 to 24 hours interval (CLr0-24);Timepoint(s) of evaluation of this end point: 30 weeks 1) 2) 3) Up to 54 weeks 4) 26 weeks 5) 6) 7) 8) | — |
Countries
Czech Republic, France, Poland, Russian Federation, United Kingdom, United States
Contacts
Public ContactMedical Information Genzyme Europe
Genzyme Europe B.V
Outcome results
None listed