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| Name | Class |
|---|---|
| Amsterdam UMC | OTHER |
| IQVIA Pty Ltd | INDUSTRY |
| IQVIA RDS Inc. | INDUSTRY |
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BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.
BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.
The study will be conducted in 2 parts: a 5-week Lead-in period (period 1) and 54 week treatment period (period 2). During period 1 all participants will receive 2 intravenous (IV) infusions of Fabrazyme®, provided by Biosidus. After that, in period 2 all participants will switch treatment to AGA BETA BS.
A total of up to 20 participants are planned for the study.
•The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker (mean serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fabrazyme® then AGA BETA BS | Experimental | The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant human alpha galactosidase A (agalsidase beta) | Drug | All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Lyso Gb3 Serum Levels | The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline. | Baseline (after 5 week lead-in period on Fabrazyme®) and 26 weeks (after the switch to AGA BETA BS) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Lyso-Gb3 Serum Levels | To evaluate the difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year (54 weeks) of treatment in participants with Fabry disease previously stabilized with Fabrazyme®, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 54 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 54 weeks (12 months) divided by serum level of the marker Lyso-Gb3 at baseline. |
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Inclusion Criteria:
Sex and Age
Male or female participant with ≥16 and ≤60 years of age at the time of signing the informed consent form (ICF).
Reproduction
Female participants who are not pregnant, breastfeeding, donating eggs (ova, oocytes), or considering becoming pregnant during the study and for 3 months after the last dose of study treatment.
All women of childbearing potential (WOCBP) must have a negative urine pregnancy test at the Screening visit and at Baseline visit (prior to the first dose of experimental intervention).
WOCBP must use one highly effective form of birth control contraception through the study and for 3 months after the last dose of study treatment.
Male participants who are not considering fathering a child during the study and for 3 months after the last dose of study treatment.
Male sexually active participant with female partner(s) of childbearing potential must agree to use male condoms during the study and for 3 months after the last dose of study treatment or have documented successful surgical sterilization.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Confirmed previous diagnosis of FD.
Participants who have been on stable Fabrazyme® treatment for at least 6 months prior to Baseline visit.
Patients that in the last 3 months before the baseline visit have been receiving ≥80% of Fabrazyme®'s labeled dose/kg, this calculation includes both infusions provided by Biosidus during the Lead in period.
Disease status considered clinically stabilized, at Investigators' discretion.
Estimated glomerular filtration rate (eGFR) ≥45 mL/minute/1.73 m2 by CKD-EPI equation at Screening visit.
If receiving pain killers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), participants must be in a stable dose for ≥ 4 weeks.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alberto A Fernández, MD | Instituto de Investigaciones Clínicas Quilmes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto de Nefrología Pergamino S.R.L | Pergamino | Buenos Aires | 2700 | Argentina | ||
| Centro Médico Santa María de la Salud |
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| ID | Title | Description |
|---|---|---|
| FG000 | Fabrazyme Then AGA BETA BS | The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks Recombinant human alpha galactosidase A (agalsidase beta): All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks Recombinant human alpha-galactosidase A (agalsidase beta): All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lead in (Fabrazyme) |
|
| ||||||||||||||||||
| Treatment Period (AGA BETA BS) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Fabrazyme Then AGA BETA BS | The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks Recombinant human alpha galactosidase A (agalsidase beta): All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks Recombinant human alpha-galactosidase A (agalsidase beta): All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 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 |
| 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 in Lyso Gb3 Serum Levels | The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline. | Differences are explained by the availability of samples collected within the correct protocol-defined window and the withdrawal of one subject before the start of the treatment period. | Posted | Mean | Standard Deviation | Nmol/L | Baseline (after 5 week lead-in period on Fabrazyme®) and 26 weeks (after the switch to AGA BETA BS) |
|
13 months
Adverse events were collected using multiple approaches to ensure completeness of safety data. Patients maintained diaries to record any adverse events occurring between visits. In addition, adverse events were systematically assessed at each scheduled study visit. Investigators also conducted follow-up telephone calls after each visit to capture any events that may have arisen in the interim.
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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 | Lead-in Period (Fabrazyme) | This is a single-arm study design where participants will serve as their own controls. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. Recombinant human alpha galactosidase A (agalsidase beta): All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Renal Atrophy | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment | Scheduled surgery (Left nephrectomy) for renal atrophy secondary to recurrent nephrolithiasis. Assesed as not related to study medication. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
This switch-over study was conducted in a small, heterogeneous cohort typical of rare-disease research. Limitations include the absence of a parallel control group, limited sample size, and a follow-up duration that may be insufficient for long-term assessment in a chronic progressive disease. These constraints are inherent to studies in rare diseases and were anticipated a priori.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nicolás Manuel Antognoni | Biosidus S.A.U. | +54 9 1140983909 | n.antognoni@biosidus.com.ar |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 22, 2024 | Nov 5, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2025 | Nov 5, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
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| ID | Term |
|---|---|
| C459420 | agalsidase beta |
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BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.
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|
| Recombinant human alpha-galactosidase A (agalsidase beta) | Drug | All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks |
|
|
| Baseline (after 5 week lead-in period on Fabrazyme®) and 54 weeks (after the switch to AGA BETA BS) |
| Change From Baseline in Pain Severity as Assessed by Brief Pain Inventory-short Form Pain Severity Items Scores | To compare the pain severity before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Brief Pain Inventory-short form (BPI). The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Change From Baseline in Pain Interference as Assessed by BPI-short Form Pain Interference Items Scores | To compare the impact of pain on daily functions before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Change From Baseline in SF-36 Health Survey Scores | To compare the participants' perception of their own health before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Short Form-36 Health Survey (SF-36). The Short Form-36 Health Survey (SF-36) is a validated patient-reported outcome instrument consisting of 36 questions designed to assess health-related quality of life. The questionnaire generates scores across eight domains (physical functioning, role limitations due to physical health, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems, and emotional well being), each scored on a 0-100 scale. Domain scores are calculated according to standard scoring algorithms, with higher scores indicating better health status and quality of life. Endpoint: Change from baseline in SF-36 scores after 26 and 54 weeks of treatment. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Blood Urea Nitrogen (BUN) Levels at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Estimated Glomerular Filtration Rate (eGFR) at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Urine Albumin-to-Creatinine Ratio at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Electrolyte and Phosphate Levels at Specified Timepoints | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Heart Rate From Electrocardiogram Assessments at Specified Timepoints | Evaluation of Heart Rate based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean PR, QRS, QT, QTcB, and QTcF Intervals at Specified Timepoints | Evaluation of PR, QRS, QT , QTcB and QTcF intervals based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Left Ventricular Wall Thickness at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Left Ventricular Mass Index at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Mean Left Ventricular Ejection Fraction at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| Number of Participants With Positive Neutralizing Antibodies at Specified Timepoints | Count of participants whose serum samples showed a neutralization percentage of agalsidase beta activity greater than 50%, the predefined threshold indicating a positive result for neutralizing antibodies. Neutralizing antibody activity was evaluated using blood samples collected at Baseline, Week 14, Week 26, and Week 54. Participants with neutralization values exceeding the 50% cutoff were classified as positive for neutralizing antibodies at each timepoint. | Baseline (after 5 week lead-in period on Fabrazyme®),14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
| San Isidro |
| Buenos Aires |
| 1642 |
| Argentina |
| Instituto de Investigaciones Clínicas Quilmes | Buenos Aires | Argentina |
| Clínica Universitaria Reina Fabiola | Córdoba | X5004 | Argentina |
| Centro Oncológico Riojano Integral | La Rioja | F5300 | Argentina |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | Centimeters |
|
| Weight | Mean | Standard Deviation | Kilograms |
|
| BMI | Mean | Standard Deviation | Kg/m2 |
|
| Fabry disease Phenotype | Fabry disease phenotype was assessed for each participant based on information available in the medical record, including previously performed genetic analyses and documented clinical evolution. Clinical information, including disease manifestations and organ involvement, was reviewed from the participant's medical history. Phenotype classification was assigned by the Principal Investigator at each study site based on the available genetic and clinical information. | Count of Participants | Participants |
|
The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks
Recombinant human alpha galactosidase A (agalsidase beta): All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks
Recombinant human alpha-galactosidase A (agalsidase beta): All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks
| OG001 | Fabrazyme Then AGA BETA BS (Per Protocol Population) | Per Protocol set will include all participants who satisfactorily complete the study and comply with the requirements of the protocol. It is a subset of the ITT population without any major/Critical protocol deviations impacting the primary endpoint of the study. |
|
|
|
| Secondary | Change From Baseline in Lyso-Gb3 Serum Levels | To evaluate the difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year (54 weeks) of treatment in participants with Fabry disease previously stabilized with Fabrazyme®, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 54 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 54 weeks (12 months) divided by serum level of the marker Lyso-Gb3 at baseline. | Differences are explained by the availability of samples collected within the correct visit window, the withdrawal of one subject before the start of the treatment period, and the discontinuation of one subject due to pregnancy before the Week 54 study visit. | Posted | Mean | Standard Deviation | Nmol/L | Baseline (after 5 week lead-in period on Fabrazyme®) and 54 weeks (after the switch to AGA BETA BS) |
|
|
|
|
| Secondary | Change From Baseline in Pain Severity as Assessed by Brief Pain Inventory-short Form Pain Severity Items Scores | To compare the pain severity before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Brief Pain Inventory-short form (BPI). The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
|
| Secondary | Change From Baseline in Pain Interference as Assessed by BPI-short Form Pain Interference Items Scores | To compare the impact of pain on daily functions before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment. | The difference in N reflects the discontinuation of one subject due to pregnancy before week 54 visit and the availability of determinations that were either missing at specific visits or collected outside the correct protocol-defined window. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
|
| Secondary | Change From Baseline in SF-36 Health Survey Scores | To compare the participants' perception of their own health before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Short Form-36 Health Survey (SF-36). The Short Form-36 Health Survey (SF-36) is a validated patient-reported outcome instrument consisting of 36 questions designed to assess health-related quality of life. The questionnaire generates scores across eight domains (physical functioning, role limitations due to physical health, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems, and emotional well being), each scored on a 0-100 scale. Domain scores are calculated according to standard scoring algorithms, with higher scores indicating better health status and quality of life. Endpoint: Change from baseline in SF-36 scores after 26 and 54 weeks of treatment. | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
|
| Secondary | Mean Blood Urea Nitrogen (BUN) Levels at Specified Timepoints | The differences in N across visits reflect the discontinuation of one subject due to pregnancy before week 54 visit and the availability of laboratory determinations at each scheduled visit. | Posted | Mean | Standard Deviation | mmol/L | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Estimated Glomerular Filtration Rate (eGFR) at Specified Timepoints | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | ml/min/1.73m2 | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Urine Albumin-to-Creatinine Ratio at Specified Timepoints | The differences in N across visits reflect the discontinuation of one subject due to pregnancy and the availability of laboratory determinations at each scheduled visit. | Posted | Mean | Standard Deviation | g/mol | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Electrolyte and Phosphate Levels at Specified Timepoints | The differences in N across visits reflect the discontinuation of one subject due to pregnancy and the availability of laboratory determinations at each scheduled visit. | Posted | Mean | Standard Deviation | mmol/L | Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Heart Rate From Electrocardiogram Assessments at Specified Timepoints | Evaluation of Heart Rate based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | Beats/min | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean PR, QRS, QT, QTcB, and QTcF Intervals at Specified Timepoints | Evaluation of PR, QRS, QT , QTcB and QTcF intervals based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks. | The differences in N across visits reflect the discontinuation of one subject due to pregnancy and the availability of determinations at each scheduled visit. | Posted | Mean | Standard Deviation | msec | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Left Ventricular Wall Thickness at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | mm | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Left Ventricular Mass Index at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | The differences in N across visits reflect the discontinuation of one subject due to pregnancy and the availability of determinations at each scheduled visit. | Posted | Mean | Standard Deviation | g/m² | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Mean Left Ventricular Ejection Fraction at Specified Timepoints | Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks. | The difference in N at Week 54 is explained by the discontinuation of one subject due to pregnancy. | Posted | Mean | Standard Deviation | percentage of ejection fraction | Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| Secondary | Number of Participants With Positive Neutralizing Antibodies at Specified Timepoints | Count of participants whose serum samples showed a neutralization percentage of agalsidase beta activity greater than 50%, the predefined threshold indicating a positive result for neutralizing antibodies. Neutralizing antibody activity was evaluated using blood samples collected at Baseline, Week 14, Week 26, and Week 54. Participants with neutralization values exceeding the 50% cutoff were classified as positive for neutralizing antibodies at each timepoint. | Only one patient was considered positive throughout the study for neutralizing ADA, as it shown >50% neutralization from baseline to 54 weeks. | Posted | Count of Participants | Participants | Baseline (after 5 week lead-in period on Fabrazyme®),14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS). |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 4 |
| 20 |
| EG001 | Treatment Period (AGA BETA BS) | After completing Lead-in period, all participants will switch treatment and receive AGA BETA BS for 54 weeks. Recombinant human alpha-galactosidase A (agalsidase beta): All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks. | 0 | 19 | 5 | 19 | 17 | 19 |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment | Scheduled cholecystectomy for symptomatic cholelithiasis. Assessed as not related to study medication. |
|
| Ischaemic Stroke | Nervous system disorders | MedDRA (25.1) | Systematic Assessment | Ischaemic stroke in a hypertensive patient, adjudicated to underlying Fabry disease and assessed as not related to study medication. |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (25.1) | Systematic Assessment | Symptomatic atrial fibrillation episode requiring hospitalization, adjudicated to underlying Fabry disease and assessed as not related to study medication |
|
| Chest pain | General disorders | MedDRA (25.1) | Systematic Assessment | Chest pain episode requiring hospitalization, adjudicated to underlying Fabry disease and assessed as not related to study medication. |
|
| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment | Episode of upper urinary tract infection requiring hospitalization and intravenous antibiotic treatment, assessed as not related to study medication. |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Herpes Zoster | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Oral infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Trichomoniasis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Pyrexia (fever) | General disorders | MedDRA (25.1) | Systematic Assessment |
|
| Adverse drug reaction | General disorders | MedDRA (25.1) | Systematic Assessment | Events non specifically reported by principal investigator. |
|
| Chills | General disorders | MedDRA (25.1) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment | Event non specifically reported by principal investigator |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Gastroesophageal sphincter insufficiency | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Large intestine polyp | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Portal hypertensive gastropathy | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
|
| Drug Hypersensitivity | Immune system disorders | MedDRA (25.1) | Systematic Assessment | Event non specifically reported by principal investigator |
|
| Hypersensitivity | Immune system disorders | MedDRA (25.1) | Systematic Assessment | Event non specifically reported by principal investigator |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
|
| Hyperphagia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
|
| Hypertensive crisis | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA (25.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (25.1) | Systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
|
| Adnexa uteri pain | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
|
The Sponsor requires investigators to submit any manuscripts or abstracts for review before public release to protect proprietary information. No specific embargo period is defined in the study documents. This review requirement constitutes a disclosure restriction applicable to investigators.
| 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 |
| Mean 54 weeks Lyso-Gb3 |
|
|
| Equivalence in efficacy was evaluated at the 26-week analysis. The same statistical approach was applied at 54 weeks to further explore efficacy differences after one year of treatment with AGA BETA BS. No formal hypothesis testing was planned for this timepoint. | t-test, 2 sided | 0.01 | Geometric Mean Ratio | 0.88 | Standard Error of the Mean | 1.04 | 95 | 0.81 | 0.97 | Equivalence | Equivalence in efficacy was evaluated at the 26-week analysis. The same statistical approach was applied at 54 weeks to further explore efficacy differences after one year of treatment with AGA BETA BS. No formal hypothesis testing was planned for this timepoint. |
|
| 54 weeks |
|
|
| Mean Difference |
| Mean Difference (Final Values) |
| -0.61 |
| Standard Deviation |
| 2.28 |
| Other |
|
| 54 weeks |
|
|
| Mean Difference |
| Mean Difference (Final Values) |
| 0.03 |
| Standard Deviation |
| 2.61 |
| Other |
|
| Physical Functioning Score - Mean 54 weeks |
|
|
| Role limitations due to physical health- Mean Baseline |
|
|
| Role limitations due to physical health-Mean 26 weeks |
|
|
| Role limitations due to physical health- Mean 54 weeks |
|
|
| Role limitations due to emotional problems-Mean Baseline |
|
|
| Role limitations due to emotional problems- Mean 26 weeks |
|
|
| Role limitations due to emotional problems- Mean 54 weeks |
|
|
| Energy/fatigue- Mean Baseline |
|
|
| Energy/fatigue- Mean 26 weeks |
|
|
| Energy/fatigue - Mean 54 weeks |
|
|
| Emotional well-being - Mean Baseline |
|
|
| Emotional well-being- Mean 26 weeks |
|
|
| Emotional well-being- Mean 54 weeks |
|
|
| Social functioning- Mean Baseline |
|
|
| Social functioning- Mean 26 weeks |
|
|
| Social functioning- Mean 54 weeks |
|
|
| Pain- Mean Baseline |
|
|
| Pain- Mean 26 weeks |
|
|
| Pain- Mean 54 weeks |
|
|
| General Health-Mean Baseline |
|
|
| General Health-Mean 26 weeks |
|
|
| General Health- Mean 54 weeks |
|
|
Mean change from baseline at 54 weeks for Physical functioning domain.
For quantitative measurements, change from baseline at visit X will be calculated as:
Test Value at Visit X - Baseline Value
| Mean Difference |
| Mean Difference (Final Values) |
| -2.8 |
| Standard Deviation |
| 19.19 |
| Other |
| Mean change from baseline at 26 weeks for Role limitations due to physical health domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 2.6 | Standard Deviation | 50.62 | Other |
| Mean change from baseline at 54 weeks for Role limitations due to physical health domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 6.9 | Standard Deviation | 43.56 | Other |
| Mean change from baseline at 26 weeks for Role limitations due to emotional problems domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 19.30 | Standard Deviation | 52.49 | Other |
| Mean change from baseline at 54 weeks for Role limitations due to emotional problems domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 14.82 | Standard Deviation | 55.10 | Other |
| Mean change from baseline at 26 weeks for Energy/fatigue domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 9.2 | Standard Deviation | 23.70 | Other |
| Mean change from baseline at 54 weeks for Energy/fatigue domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 3.90 | Standard Deviation | 20.33 | Other |
| Mean change from baseline at 26 weeks for Emotional well-being domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 2.50 | Standard Deviation | 22.28 | Other |
| Mean change from baseline at 54 weeks for Emotional well-being domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | -2.2 | Standard Deviation | 22.43 | Other |
| Mean change from baseline at 26 weeks for Social functioning domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | -2.37 | Standard Deviation | 24.76 | Other |
| Mean change from baseline at 54 weeks for Social functioning domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 0.69 | Standard Deviation | 25.46 | Other |
| Mean change from baseline at 26 weeks for Pain domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 4.61 | Standard Deviation | 29.09 | Other |
| Mean change from baseline at 54 weeks for Pain domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 15.69 | Standard Deviation | 25.91 | Other |
| Mean change from baseline at 26 weeks for General health domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | 2.10 | Standard Deviation | 13.37 | Other |
| Mean change from baseline at 54 weeks for General health domain. For quantitative measurements, change from baseline at visit X will be calculated as: Test Value at Visit X - Baseline Value | Mean Difference | Mean Difference (Final Values) | -2.8 | Standard Deviation | 17.59 | Other |
|
| Mean 26 weeks Blood Urea Nitrogen |
|
|
| Mean 54 weeks Blood Urea Nitrogen |
|
|
|
| Mean 54 weeks eGFR |
|
|
|
| Mean 54 weeks Urine Albumin/Creatinine ratio |
|
|
|
| Mean 26 weeks Sodium |
|
|
| Mean 54 weeks Sodium |
|
|
| Mean Baseline Potassium |
|
|
| Mean 14 weeks Potassium |
|
|
| Mean 26 weeks Potassium |
|
|
| Mean 54 weeks Potassium |
|
|
| Mean Baseline Magnesium |
|
|
| Mean 14 weeks Magnesium |
|
|
| Mean 26 weeks Magnesium |
|
|
| Mean 54 weeks Magnesium |
|
|
| Mean Baseline Calcium |
|
|
| Mean 14 weeks Calcium |
|
|
| Mean 26 weeks Calcium |
|
|
| Mean 54 weeks Calcium |
|
|
| Mean Baseline Chloride |
|
|
| Mean 14 weeks Chloride |
|
|
| Mean 26 weeks Chloride |
|
|
| Mean 54 weeks Chloride |
|
|
| Mean Baseline Bicarbonate |
|
|
| Mean 14 weeks Bicarbonate |
|
|
| Mean 26 weeks Bicarbonate |
|
|
| Mean 54 weeks Bicarbonate |
|
|
| Mean Baseline Phosphate |
|
|
| Mean 14 weeks Phosphate |
|
|
| Mean 26 weeks Phosphate |
|
|
| Mean 54 weeks Phosphate |
|
|
|
| 54 weeks Mean ECG-assesed Heart Rate |
|
|
|
| Mean 54 weeks PR interval |
|
|
| Mean Baseline QRS interval |
|
|
| Mean 26 weeks QRS interval |
|
|
| Mean 54 weeks QRS interval |
|
|
| Mean Baseline QT interval |
|
|
| Mean 26 weeks QT interval |
|
|
| Mean 54 weeks QT interval |
|
|
| Mean Baseline QTcB interval |
|
|
| Mean 26 weeks QTcB interval |
|
|
| Mean 54 weeks QTcB interval |
|
|
| Mean Baseline QTcF interval |
|
|
| Mean 26 weeks QTcF interval |
|
|
| Mean 54 weeks QTcF interval |
|
|
|
| Mean 54 weeks Left Ventricle wall thickness |
|
|
|
| Mean 54 weeks Left Ventricular Mass Index |
|
|
|
| Mean 54 weeks Left Ventricle Ejection Fraction |
|
|
| Title | Measurements |
|---|
|
| 54 weeks |
|