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This is an exploratory study to evaluate changes in glycosphingolipid levels and other (exploratory) Fabry disease parameters in male Fabry disease participants who were previously treated with agalsidase alfa (Replagal®) 0.2 milligram per kilogram (mg/kg) every two weeks (q2w) and who are being switched to agalsidase beta (Fabrazyme®) 1.0 mg/kg q2w.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Agalsidase beta | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Agalsidase beta | Biological | Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers. | Baseline, Month 2, 4, 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Genzyme, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Coral Springs | Florida | United States | ||||
A total of 16 participants were screened of which 1 participant was screen failure. A total of 15 participants were enrolled in this study.
The study was conducted at 6 centers in the United States of America between April 30, 2012 and March 15, 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Agalsidase Beta | Commercially available agalsidase beta (Fabrazyme ®) 1.0 milligram per kilogram (mg/kg) administered as an intravenous infusion every 2 weeks (q2w) up to Month 6. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Baseline, Month 2, 4, 6 |
| Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. | Baseline, Month 2, 4, 6 |
| Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 | Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual participant listing only. | Baseline, Month 2, 4, 6 |
| Decatur |
| Georgia |
| United States |
| Baltimore | Maryland | United States |
| Grand Rapids | Michigan | United States |
| Hellertown | Pennsylvania | United States |
| Fairfax | Virginia | United States |
| COMPLETED |
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| NOT COMPLETED |
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All enrolled participants were included in the analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Agalsidase Beta | Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. |
| 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 |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| |||||||||||||||||||||||
| Duration of Fabry Disease | Duration of Fabry disease was calculated from date of initial diagnosis of Fabry disease to date of the first study infusion. Number of participants analyzed for this baseline measure were 14, as one participant did not have information on date of initial diagnosis of Fabry disease. | Median | Full Range | years |
| |||||||||||||||||||||
| Method of Diagnosis of Fabry Disease | Number of participants with each method (genotype, leukocyte alfa-galactosidase A [GAL] activity, and plasma alfa-GAL activity) are reported. Some participants were diagnosed by more than 1 method, hence reported under more than 1 category. | Number | participants |
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| 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 | Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers. | All enrolled participants were included in the analysis. Here, 'n' signifies participants with plasma Lyso-GL-3 assessment at the specified time point. | Posted | Mean | Standard Deviation | percent change | Baseline, Month 2, 4, 6 |
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| Secondary | Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. | All enrolled participants were included in the analysis. Here, 'n' signifies participants with plasma GL-3 assessment at the specified time point. | Posted | Mean | Standard Deviation | percent change | Baseline, Month 2, 4, 6 |
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| Secondary | Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 | Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. | All enrolled participants were included in the analysis. Here, 'n' signifies participants with urine GL-3 assessment at the specified time point. | Posted | Median | Full Range | percent change | Baseline, Month 2, 4, 6 |
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| Secondary | Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 | Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual participant listing only. | The data for this outcome measure was exploratory and to be collected in individual participant listing only. Analysis of this data was planned only if baseline data was collected on a large number of enrolled participants. This was not the case and therefore interpretation of these results were not possible. | Posted | Baseline, Month 2, 4, 6 |
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Baseline up to end of study (Month 6) or early withdrawal
All enrolled participants were included in the analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Agalsidase Beta | Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion every 2 weeks up to Month 6. | 0 | 15 | 1 | 15 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion-associated reactions | General disorders | MedDRA 16.0 | Non-systematic Assessment |
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This is considered to be an exploratory study for the following reasons: it was based on a small number of participants and has been designed as an open-label, single-arm study as opposed to a two-arm crossover design.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | 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 |
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| ID | Term |
|---|---|
| C459420 | agalsidase beta |
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| Other |
|
| Plasma alfa-GAL activity |
|
| Title | Measurements |
|---|---|
|
| <0.0001 |
| No |
| Superiority or Other |
| Baseline versus Month 6: Analysis was performed using one sample t-test. | One sample t-test | <0.0001 | No | Superiority or Other |
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