Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ402671 in Treatment-naïve Adult Male Patients with Fabry Disease

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-005324-41-GB
• Date of registration: 30/06/2014
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ402671 in Treatment-naïve Adult Male Patients with Fabry Disease
• Scientific 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
• Date of first enrolment: 07/10/2014
• Target sample size: 8
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005324-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Poland, Russian Federation, United Kingdom, United States

Contacts

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V

Key inclusion & exclusion criteria

Inclusion criteria:
The patient is =18 years of age and <50 years of age.
The patient is male.
The patient has provided a signed informed consent.
The patient had a confirmed diagnosis of Fabry disease as documented by leukocyte a-Galactosidase A (aGAL) activity of <4 nmol/hr/mg leukocyte (preferred assay; results from a central laboratory) or plasma aGAL <1.5 nmol/hr/mL (results from a central laboratory).
The patient has a plasma globotriaosylsphingosine (lyso-GL3) >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:
The patient has an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 using (Chronic Kidney Disease Epidemiology Collaboration) CKD-EPI.
The patient has 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 21 day period). All 3 samples must be collected regardless of the results and results available prior to Day 1.
The patient had undergone a kidney transplant.
The patient has 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 patient has 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 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.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease
MedDRA version: 17.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

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 milligram(s)
Concentration type: equal
Concentration number: 4-

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 milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Primary end point(s): Change from baseline in globotriaosylceramide (GL-3) scores as evaluated by light microscopy (LM) in superficial skin capillary

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: 26 weeks

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 Outcome(s)

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)

Secondary ID(s)

ACT13739

Source(s) of Monetary Support

Genzyme Corporation