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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02228460
Recruitment Status : Completed
First Posted : August 29, 2014
Last Update Posted : September 11, 2017
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief 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.

Condition or disease Intervention/treatment Phase
Fabry's Disease Drug: GZ/SAR402671 Phase 2

Detailed Description:
The total duration of study per participant was 7 to 8 months for participants who entered a planned extension study and approximately 13 to 14 months for participants who did not enter a planned extension study. A 2-year extension study was planned for eligible participants.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Enzyme Replacement Therapy (ERT) Treatment-naïve Adult Male Patients Diagnosed With Fabry Disease
Study Start Date : November 2014
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: GZ/SAR402671
GZ/SAR402671 15 mg once daily orally for 26 weeks.
Drug: GZ/SAR402671
Pharmaceutical form: Capsule; Route of administration: Oral

Primary Outcome Measures :
  1. Change from baseline in globotriaosylceramide (GL-3) scores as evaluated by light microscopy (LM) in superficial skin capillary endothelium [ Time Frame: 26 weeks ]

Secondary Outcome Measures :
  1. Change from baseline in plasma GL-3, lyso GL-3, and glucosylceramide (GL-1) [ Time Frame: Baseline, 30 weeks ]
  2. Change from baseline in scores of GL-3 from other cell types in skin biopsy using LM [ Time Frame: Baseline, 30 weeks ]
  3. Urine GL-3 change from baseline [ Time Frame: Baseline, 30 weeks ]
  4. Characterization of the safety profile of GZ402671, including the frequency, duration, and severity of adverse events (AEs) [ Time Frame: Up to 54 weeks ]
  5. Assessment PK parameters - peak concentration (Cmax), Dose-Corrected Observed Plasma Trough Concentrations (Ctrough), and time to reach max concentration (tmax) [ Time Frame: 26 weeks ]
  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) [ Time Frame: 26 weeks ]
  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) [ Time Frame: 26 weeks ]
  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) [ Time Frame: 26 weeks ]

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • The participant was ≥18 years of age and <50 years of age.
  • The participant was male.
  • The participant had provided a signed informed consent.
  • The participant had a confirmed diagnosis of Fabry disease as documented by leukocyte α- Galactosidase A (αGAL) activity of <4 nmol/hour/mg leukocyte (preferred assay; results from a central laboratory) or plasma αGAL <1.5 nmol/hr/mL (results from a central laboratory).
  • The participant had a plasma globotriaosylsphingosine (lyso-GL3) greater than or equal to 65 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) <60 mL/min/1.73 m^2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
  • The participant had a median urine protein/creatinine ratio (PCR) ≥0.5 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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02228460

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United States, Georgia
Investigational Site Number 840002
Atlanta, Georgia, United States, 30322
United States, Ohio
Investigational Site Number 840003
Cincinnati, Ohio, United States, 45229
United States, Virginia
Investigational Site Number 840001
Fairfax, Virginia, United States, 22030
Investigational Site Number 203001
Praha 2, Czechia, 12808
Investigational Site Number 250001
Garches, France, 92380
Investigational Site Number 616001
Warszawa, Poland, 04-730
Russian Federation
Investigational Site Number 643002
Moscow, Russian Federation, 125167
United Kingdom
Investigational Site Number 826003
Birmingham, United Kingdom, B15 2TH
Investigational Site Number 826002
Cambridge, United Kingdom, CB2 OQQ
Investigational Site Number 826004
London, United Kingdom, NW1 2PJ
Investigational Site Number 826001
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Genzyme, a Sanofi Company
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Genzyme, a Sanofi Company Identifier: NCT02228460     History of Changes
Other Study ID Numbers: ACT13739
U1111-1152-1456 ( Other Identifier: UTN )
First Posted: August 29, 2014    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: September 2016
Additional relevant MeSH terms:
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Fabry Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders