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Phase 2 N=11 Treatment

Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease

Fabry Disease

Enrolled (actual)
11
Serious AEs
27.3%
Results posted
Dec 2019
Primary outcome: Primary: Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26 — 4; 1; 3; 1 Participants — p=0.3173

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
GZ/SAR402671 (Drug)
Age
Adult · 18+ yrs
Sex
Male
Sponsor
Genzyme, a Sanofi Company
Primary completion
Sep 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
4; 1; 3; 1 0.3173
PRIMARY
Mean Change From Baseline at Week 26 in Skin GL-3 Score in Superficial Skin Capillary Endothelium
-0.22 0.625
SECONDARY
Change From Baseline in Plasma GL-3 Concentration at Week 26
-3.62
SECONDARY
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso-GL-3) Concentration at Week 26
-30.99
SECONDARY
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration at Week 26
-3.26
SECONDARY
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Endothelial Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
1; 2; 6
SECONDARY
Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
2; 7
SECONDARY
Change From Baseline at Week 26 in Skin GL-3 Score in Perineurium Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
1; 8
SECONDARY
Change From Baseline in Urine Globotriaosylceramide (GL-3) Concentration at Week 26
-0.25
SECONDARY
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
9
SECONDARY
Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671
24.7; 192.0
SECONDARY
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671
152.0; 165.0; 182.0; 164.0; 175.0; 164.0
SECONDARY
PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671
8.00; 4.00
SECONDARY
PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671
476; 4110
SECONDARY
PK: Terminal Half-life (t1/2z) of GZ/SAR402671
86.8; 128.0
SECONDARY
PK: Apparent Total Body Clearance of GZ/SAR402671 at Steady State (CLss/F)
7490
SECONDARY
PK: Apparent Volume of Distribution of GZ/SAR402671 (Vss/F) at Steady State
SECONDARY
PK: Cumulated Amount of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (Ae0-24)
3210.0
SECONDARY
PK: Percentage of Dose of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (fe0-24)
21.4
SECONDARY
PK: Renal Clearance (CLR) of GZ/SAR402671 From 0 to 24 Hours
925

Summary

Primary Objective: To assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and exploratory efficacy of GZ/SAR402671 in enzyme replacement therapy treatment-naïve adult male participants diagnosed with Fabry disease.

Eligibility Criteria

Inclusion criteria

  • The participant was greater than equal to (>=) 18 years of age and less than ( =65 nanogram per milliliter (ng/mL).
  • The participant had never been treated with a Fabry disease-specific treatment.
  • If the participant was on renin-angiotensin-aldosterone system (RAAS) blockers and antidepressants, the dose should be stable (i.e., prescribed dose and frequency) for at least the immediate 3 months prior to screening.

Exclusion criteria

  • The participant had an estimated glomerular filtration rate (eGFR) =0.5 gram per gram (g/g) (median of 3 overnight urine collections. Collection of each of the 3 samples must occur between 4 and 7 days of each other, and all samples must be collected within a 15 day period). All 3 samples must be collected regardless of the results and results available prior to Day 1.
  • The participant had undergone a kidney transplant.
  • The participant had either active or a history of clinically significant organic disease (with the exception of the symptoms related to Fabry disease), including clinically significant cardiovascular, hepatic, pulmonary, hematologic, neurological or renal disease, or other medical condition, serious inter-current illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial.
  • The participant had abnormal liver function (serum total bilirubin > the upper limit of normal, or serum alanine aminotransferase ([ALT] and aspartate aminotransferase [AST] >2.0 times the upper limit of normal).
  • The participant had, 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 millimeter (mm) (Grade PSC-2). Participants with nuclear cataracts were not excluded.
  • The participant was currently receiving potentially cataractogenic medications.
  • The participant had received strong or moderate inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) per Food and Drug Administration (FDA) classification within 14 days prior to enrollment or within 5 times the elimination half-life or PD half-life of the medication, whichever is longer.
  • The participant was scheduled for in-patient hospitalization, including elective surgery, during the study.
  • The participant had 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). Participants with a positive hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B immunization were eligible if other criteria met (i.e., negative tests for: HBsAg, hepatitis B core antibody [HBcAb], and hepatitis C virus antibody [HCVAb]).
  • The participant had participated in a study involving an investigational drug within the past 30 days of the start of the trial.
  • The participant was unwilling to comply with the requirements of the protocol.
  • The participant was a sexually active man who was not willing to use 2 forms of birth control including a barrier method during the study until 6 weeks after the last treatment with investigational medicinal product (IMP).
  • The participant had a history or ongoing clinically significant cardiac arrhythmia, defined as either atrial fibrillation, sustained or non-sustained ventricular tachycardia.
  • The participant had any contraindication to magnetic resonance imaging (MRI).
  • The participant had one of the following central nervous system exclusion criteria:
  • Acute stroke, within 3 months of the screening visit.
  • History of seizures.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02228460). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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