Fabry DiseasePhase 2NCT02228460
Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease
A Phase 2 study testing GZ/SAR402671 in people with Fabry Disease, run by Genzyme, a Sanofi Company at 8 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 years, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- GZ/SAR402671
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 8 sitesin 5 countries
- Study dates
- Nov 2014to Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
United States3 sites
Investigational Site Number 840002
Atlanta, Georgia, 30322
Investigational Site Number 840003
Cincinnati, Ohio, 45229
Investigational Site Number 840001
Fairfax, Virginia, 22030
United Kingdom2 sites
Investigational Site Number 826003
Birmingham, B15 2TH
Investigational Site Number 826002
Cambridge, CB2 OQQ
About this study
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
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.
Read the 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
- Being tested
- GZ/SAR402671
- Keywords
- Venglustat
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GZ/SAR402671Drug
Pharmaceutical form: Capsule; Route of administration: Oral
| Study group | Role | What they receive |
|---|---|---|
| GZ/SAR402671 | Experimental | GZ/SAR402671 15 milligram (mg) once daily orally for 26 weeks. Receives: Drug: GZ/SAR402671 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Measured: Baseline, Week 26
Mean Change From Baseline at Week 26 in Skin GL-3 Score in Superficial Skin Capillary Endothelium
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Change from Baseline in GL-3 score was obtained by subtracting Baseline value from post-baseline value at Week 26. A negative change from Baseline indicates less severe condition at Week 26.
Measured: Baseline, Week 26
Secondary outcomes (18)
Change From Baseline in Plasma GL-3 Concentration at Week 26
Change from Baseline in plasma GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-3 in plasma was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
Measured: Baseline, Week 26
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso-GL-3) Concentration at Week 26
Change from Baseline in plasma Lyso-GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of lyso-GL-3 in plasma was determined using a validated LC-MS/MS method.
Measured: Baseline, Week 26
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration at Week 26
Change from Baseline in plasma GL-1 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-1 in plasma was determined using a validated LC-MS/MS method.
Measured: Baseline, Week 26
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
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Measured: Baseline, Week 26
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
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Measured: Baseline, Week 26
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
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Measured: Baseline, Week 26
Change From Baseline in Urine Globotriaosylceramide (GL-3) Concentration at Week 26
Change from Baseline in urine GL-3 was obtained by subtracting Baseline value from post-baseline value at Week 26. Concentration of GL-3 in urine was determined using a validated LC-MS/MS method.
Measured: Baseline, Week 26
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened during on-treatment period (period from the first administration of study drug through the last administration of the study drug plus 30 days or end of study participation for participant, whichever occurs first).
Measured: From Baseline up to 212 days
Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671
Maximum plasma concentration observed for study drug was reported.
Measured: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671
Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.
Measured: Predose on Days 14, 28, 56, 84, 126, and 182
PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671
Tmax was defined as time to reach maximum plasma concentration of study drug.
Measured: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671
Area under the plasma concentration versus time curve of study drug from time 0 to 24 hours (AUC0-24) was calculated using the trapezoidal method over the dosing interval.
Measured: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Terminal Half-life (t1/2z) of GZ/SAR402671
Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half. The t1/2z was estimated based on 24-hour post-dose PK.
Measured: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Apparent Total Body Clearance of GZ/SAR402671 at Steady State (CLss/F)
Apparent total body clearance at steady state was a quantitative measure of rate of clearance of drug from the blood following oral administration, and is described in terms of volume of fluid clear of drug per time unit (eg, mL/min).
Measured: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182
PK: Apparent Volume of Distribution of GZ/SAR402671 (Vss/F) at Steady State
Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of drug.
Measured: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182
PK: Cumulated Amount of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (Ae0-24)
Ae0-24 was the cumulated amount of study drug excreted in urine during the time interval of 0 to 24 hours.
Measured: 0-24 hours on Day 182
PK: Percentage of Dose of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (fe0-24)
fe0-24 was the fraction of dose excreted in urine during the time interval of 0 to 24 hours.
Measured: 0-24 hours on Day 182
PK: Renal Clearance (CLR) of GZ/SAR402671 From 0 to 24 Hours
CLR was calculated by dividing the cumulative amount of drug excreted in urine during the dosing interval of 0-24 hours by area under the plasma drug concentration time-curve during the dosing interval of 0-24 hours.
Measured: 0-24 hours on Day 182
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study startNov 2014
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228460
- Sponsor's protocol ID
- ACT13739
- Other IDs
- 2013-005324-41, U1111-1152-1456
- Status last verified
- Sep 2016
- First submitted
- 27 Aug 2014
- Last updated
- 17 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36481125
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02228460
- Acronym / sponsor ID
- ACT13739
- Conditions
- Fabry Disease
- Keywords
- Venglustat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2014 (actual)
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 29 Aug 2014 (estimated)
- Results
- Posted 17 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GZ/SAR402671 | Experimental | Drug: GZ/SAR402671GZ/SAR402671 15 milligram (mg) once daily orally for 26 weeks. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GZ/SAR402671Pharmaceutical form: Capsule; Route of administration: Oral | Drug | GZ/SAR402671 |
Primary outcome
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
Time frame: Baseline, Week 26
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Mean Change From Baseline at Week 26 in Skin GL-3 Score in Superficial Skin Capillary Endothelium
Time frame: Baseline, Week 26
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Change from Baseline in GL-3 score was obtained by subtracting Baseline value from post-baseline value at Week 26. A negative change from Baseline indicates less severe condition at Week 26.
18 secondary outcomes
Change From Baseline in Plasma GL-3 Concentration at Week 26
Time frame: Baseline, Week 26
Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso-GL-3) Concentration at Week 26
Time frame: Baseline, Week 26
Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration at Week 26
Time frame: Baseline, Week 26
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
Time frame: Baseline, Week 26
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
Time frame: Baseline, Week 26
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
Time frame: Baseline, Week 26
Change From Baseline in Urine Globotriaosylceramide (GL-3) Concentration at Week 26
Time frame: Baseline, Week 26
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From Baseline up to 212 days
Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671
Time frame: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671
Time frame: Predose on Days 14, 28, 56, 84, 126, and 182
PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671
Time frame: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671
Time frame: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Terminal Half-life (t1/2z) of GZ/SAR402671
Time frame: Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose)
PK: Apparent Total Body Clearance of GZ/SAR402671 at Steady State (CLss/F)
Time frame: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182
PK: Apparent Volume of Distribution of GZ/SAR402671 (Vss/F) at Steady State
Time frame: Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182
PK: Cumulated Amount of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (Ae0-24)
Time frame: 0-24 hours on Day 182
PK: Percentage of Dose of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (fe0-24)
Time frame: 0-24 hours on Day 182
PK: Renal Clearance (CLR) of GZ/SAR402671 From 0 to 24 Hours
Time frame: 0-24 hours on Day 182
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36481125Deegan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GZ/SAR402671 in people with Fabry Disease, run by Genzyme, a Sanofi Company at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, United Kingdom, France, Poland, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline, Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02228460, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.