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

NCT ID: NCT02228460

Last Updated: 2019-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-09-30

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.

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.

Conditions

Fabry Disease

Keywords

Venglustat

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GZ/SAR402671

GZ/SAR402671 15 milligram (mg) once daily orally for 26 weeks.

Group Type: EXPERIMENTAL

GZ/SAR402671

Intervention Type: DRUG

Pharmaceutical form: Capsule; Route of administration: Oral

Interventions

GZ/SAR402671

Pharmaceutical form: Capsule; Route of administration: Oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The participant was greater than equal to (>=) 18 years of age and less than (<) 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 nanomole/hour/milligram (nmol/hr/mg) leukocyte (preferred assay; results from a central laboratory) or plasma αGAL <1.5 nanomole/hour/milliliter (nmol/hr/mL) (results from a central laboratory).
• The participant had a plasma globotriaosylsphingosine (lyso-GL3) >=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) <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 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).

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840002

Atlanta, Georgia, United States

Investigational Site Number 840003

Cincinnati, Ohio, United States

Investigational Site Number 840001

Fairfax, Virginia, United States

Investigational Site Number 250001

Garches, , France

Investigational Site Number 616001

Warsaw, , Poland

Investigational Site Number 643002

Moscow, , Russia

Investigational Site Number 826003

Birmingham, , United Kingdom

Investigational Site Number 826002

Cambridge, , United Kingdom

Countries

Czechia; United States; France; Poland; Russia; United Kingdom

References

Deegan PB, Goker-Alpan O, Geberhiwot T, Hopkin RJ, Lukina E, Tylki-Szymanska A, Zaher A, Sensinger C, Gaemers SJM, Modur V, Thurberg BL, Sharma J, Najafian B, Mauer M, DasMahapatra P, Wilcox WR, Germain DP. Venglustat, an orally administered glucosylceramide synthase inhibitor: Assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study. Mol Genet Metab. 2023 Feb;138(2):106963. doi: 10.1016/j.ymgme.2022.11.002. Epub 2022 Nov 9.

Reference Type: DERIVED

PMID: 36481125 (View on PubMed)

Other Identifiers

2013-005324-41

Identifier Type: -

Identifier Source: secondary_id

U1111-1152-1456

Identifier Type: OTHER

Identifier Source: secondary_id

ACT13739

Identifier Type: -

Identifier Source: org_study_id