Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005324-41 | |||
| U1111-1152-1456 | Other Identifier | UTN |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GZ/SAR402671 | Experimental | GZ/SAR402671 15 milligram (mg) once daily orally for 26 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GZ/SAR402671 | Drug | Pharmaceutical form: Capsule; Route of administration: Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline, Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 26 |
Not provided
Inclusion criteria:
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).
The participant had one of the following central nervous system exclusion criteria:
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 840002 | Atlanta | Georgia | 30322 | United States | ||
| Investigational Site Number 840003 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36481125 | Derived | 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. |
Not provided
Not provided
Out of 14 screened participants, 11 participants were enrolled and treated in the study.
Participants were enrolled in the study at 8 centers in 5 countries between 11 November 2014 and 06 September 2016. A total of 14 participants were screened in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | GZ/SAR402671 | GZ/SAR402671 15 milligram (mg) once daily, orally for 26 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. |
| 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 0-24 hours on Day 182 |
| Cincinnati |
| Ohio |
| 45229 |
| United States |
| Investigational Site Number 840001 | Fairfax | Virginia | 22030 | United States |
| Investigational Site Number 250001 | Garches | 92380 | France |
| Investigational Site Number 616001 | Warsaw | 04-730 | Poland |
| Investigational Site Number 643002 | Moscow | 125167 | Russia |
| Investigational Site Number 826003 | Birmingham | B15 2TH | United Kingdom |
| Investigational Site Number 826002 | Cambridge | CB2 OQQ | United Kingdom |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Analysis was performed on full analysis set (FAS) that included all participants who received at least 1 dose of study treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | GZ/SAR402671 | GZ/SAR402671 15 mg once daily, orally for 26 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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. | Analysis was performed on full analysis set (FAS) that included all participants who received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Count of Participants | Participants | Baseline, Week 26 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, Week 26 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Mean | Standard Deviation | mcg/mL | Baseline, Week 26 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Week 26 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Mean | Standard Deviation | mcg/mL | Baseline, Week 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 | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Count of Participants | Participants | Baseline, Week 26 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Count of Participants | Participants | Baseline, Week 26 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Count of Participants | Participants | Baseline, Week 26 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26. | Posted | Mean | Standard Deviation | mg/mmol Cr | Baseline, Week 26 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Analysis was performed on safety population which included all enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From Baseline up to 212 days |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671 | Maximum plasma concentration observed for study drug was reported. | Analysis was performed on PK population which included all participants for whom the primary PK data were considered sufficient and interpretable. Here, 'number analyzed' = participants with available data at specified time-point. | Posted | Mean | Standard Deviation | ng/mL | 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) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point. | Posted | Mean | Standard Deviation | ng/mL | Predose on Days 14, 28, 56, 84, 126, and 182 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point. | Posted | Median | Full Range | hours | 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) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point. | Posted | Mean | Standard Deviation | ng*hour/mL | 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) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'number analyzed' = participants with available data at specified time-point. | Posted | Mean | Standard Deviation | hours | 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) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | mL/hour | Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Since the percent extrapolation of AUC for all participants was >30%, AUC could not be determined and hence, Vss/F could not be calculated. | Posted | Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | mcg | 0-24 hours on Day 182 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | percentage of dose | 0-24 hours on Day 182 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | mL/hour | 0-24 hours on Day 182 |
|
|
Baseline up to 212 days
Reported AEs are TEAEs that is AEs developed/worsened during "on treatment period" (from first administration through last administration of study drug + 30 days or end of study participation for participant, whichever occurs first). Analysis was performed on safety population that included all enrolled participants who received at least 1 dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GZ/SAR402671 | GZ/SAR402671 15 mg once daily, orally for 26 weeks. | 0 | 11 | 3 | 11 | 9 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Floppy infant | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Blepharitis | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Chalazion | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Lenticular opacities | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Retinal vascular disorder | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oesophageal discomfort | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Electrocardiogram T wave abnormal | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Nuclear magnetic resonance imaging brain abnormal | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Vibration test abnormal | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| White matter lesion | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Angiokeratoma | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | 800-633-1610 | 1# | Contact-US@sanofi.com |
| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000608118 | venglustat |
Not provided
Not provided
Not provided
| Baseline Score: 2 / Week 26 Score: 2 |
|
|
|
|
|
|
|
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Day 14 |
|
| ||||
| Day 28 |
|
| ||||
| Day 56 |
|
| ||||
| Day 84 |
|
| ||||
| Day 126 |
|
| ||||
| Day 182 |
|
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|